The present research work summarizes the current knowledge of the pathogenic role of oxidative stress in the onset and progression of diabetes and its complications and presents the results of studies aimed at modulating oxidative stress through the use of anti oxidants such as [Acetyl-L-Carnitine, a-Lipoic acid, Beta Carotene, Chromium, Magnesium, Vanadyl Sulfate, Zinc, Coenzyme Q10, N-Acetyl Cysteine, vitamin E, and Lycopene] to ascertain whether significantly modifies oxidative status in patients with type 2. This study was conducted from February 2007 to May 2009 on persons clinically diagnosed of diabetes (Random sample of 313 who had primary Type 2 Diabetic subjects). A total of [282] patients of [301] T2DM were completed the phase II of observational baseline study whom randomly segregated into 12 groups: Each group contains in between [23-24] patients. All participants were directly clinically interviewed; similar questionnaire, measurements, investigations were applied. After 9 months of treatment, the mean of VAS scores for pain were significantly reduced from baseline in acetyl-carnitine-treated patients (p < 0.0 vs baseline) compared with 8% in baseline recipients, a significant reduction in the mean TSS and its subscores for stabbing/lancinating and burning pain was observed in all active arms compared with the corresponding arm (all P < 0.05). Pain as the most bothersome symptom showed significant improvement in study and in taking 1,000 mg ALC. The O’Brien’s rank scores for all vibratory parameters revealed significant improvements in patients treated with 1,000 mg ALC t.i.d. when compared with corresponding (1,300 ± 571 vs. 1,452 ± 571, P = 0.007). The greatest changes in NCV (at 9 months) were observed in the sensory sural nerve (7 m/sec in the acetylcarnitine group vs +1.0 m/sec in the baseline group), sensory ulnar nerve (+2.9 vs +0.1 m/sec, respectively) and motor peroneal nerve (+2.7 vs -0.2 m/sec), whereas the greatest changes in amplitude were recorded in the motor peroneal nerve (+2.2 vs +0.1 mV). Mean baseline neuropathic impairment scores decreased in the ALA groups versus corresponding (P = 0.02). The total scale of the Hamburg Pain Adjective List (HPAL) was significantly reduced in ALA 1,200 and ALA 600 compared with corresponding after 9 months (both P < 0.01). A similar significant improvement in NSC number, severity, and change was found in all ALA groups compared with the corresponding group (all P < 0.05, except for NSC number in ALA1800: P = 0.08). The Neuropathy Disability Score decreased but was significant only for the 1,200-mg group versus the Abstract -XVI- corresponding group (P = 0.030). QTc interval at 3 months was shorter in chromium group (406 +/- 35 milliseconds) than in corresponding group (431 +/- 26 milliseconds, P = .01). That CoQ supplementation improved endothelial function of the brachial artery in patients with type 2 diabetes. The main effect of CoQ significantly decreased systolic (-6.1±2.6 mmHg, P=0.021) and diastolic (-2.9±1.4 mmHg, P=0.048) blood pressure. After 9 months of treatment, the vitamin E supplementation had significant increases in median motor nerve conduction velocity (P = 0.0019), and the tibial motor nerve distal latency decreased significantly (P = 0.0284). The level of systolic blood pressure significantly decreased (P< 0.05) after 6 month of treatment with vitamin E 1200 UI daily. Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. In the present study, there were no decreases in serum lipid and lipoprotein levels in type 2 diabetic patients who were given vitamins E and of magnesium, zinc, suggesting that these antioxidants do not act through reducing lipid profiles in protecting renal cells and decreasing microalbuminuria.The effect of these antioxidants in reducing MDA, as a known confounder of nephropathy in type 2 diabetes. Thus, the attenuation of microalbuminuria by these antioxidants may be linked to their antioxidant activity and inhibition of lipid peroxidation. This study demonstrate that ALC treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy. The results of my study demonstrate that alpha-lipoic acid appears to be an effective drug in the treatment for not only peripheral and autonomic diabetic neuropathy.This study shows that defective nerve conduction in diabetic subjects with mild-to-moderate peripheral neuropathy may be improved by pharmacological doses of vitamin E supplementation. The results of the present study indicated that in type 2 diabetic patients a vitamin E or Mg and Zn, might decrease blood pressure. Among the most important minerals for supplementation are chromium, magnesium, and vanadium. NAC administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes via reduction of oxidative stress. The results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients. Zinc supplementation for type 2 diabetic patients had beneficial effect in elevating their serum zinc level and improving their glycemic control that shown by decreasing HbA1c% concentrations. Here, that therapy with high-dose AT significantly decreases PAI-1 while Vitamin E supplementation also decreases plasma C-RP levels, suggesting a decrease in proinflammatory activity.