Fifty-one non insulin dependant diabetes mellitus (NIDDM) patients and thirty-one age and sex matched control subjects were included in this study in an attempt to clarify the role of dyslipidemia and oxidative modification of lipoproteins in the pathogenesis of diabetic polyneuropathy.Peripheral nerve dysfunction was evaluated by clinical examination, and electrophysiological testing of the somatosensory and autonomic peripheral nerves. Blood samples were drawn (after 12 hours fasting) for biochemical analysis of blood lipid components [total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL)], oxidized lipid components (oxidized LDL/VLDL and oxidized HDL), and serum peroxynitrite level. The atherogenic indices were also calculated. Sensory responses and the minimum and maximum sensory refractory period were recorded from the right ulnar and sural nerves. Motor responses and the minimal F-wave latency were recorded from the right ulnar and common peroneal nerves. The sympathetic skin responses (SSR) evoked by electrical stimulation of the right median and common peroneal nerves were also recorded and analyzed. The diabetic group showed significant reduction in the sensory and motor amplitude and nerve conduction velocity with a significant prolongation of the distal motor latency, minimum F-wave latency, and minimum sensory refractory period. The maximum sensory refractory period and the duration of the sensory and motor responses were within the normal limits. Abnormal reduction of the sensory and motor NCV was significantly correlated to the severity and duration of hyperglycemia. The dyslipidemia in our diabetic patients characterized by a significant reduction of HDL, and insignificant elevation of TG, TC, and VLDL levels. The LDL level was comparable to that in the control subjects. Non of above lipoprotein fractions was related to any of the electrophysiological parameters of diabetic neuropathy. A significant elevation of atherogenic indices was observed in our patients, however, these indices showed little or no association with diabetic polyneuropathy (indicated by a reduction in the NCV). The oxidized low density lipoprotein/very low density lipoprotein was elevated in our neuropathic diabetic patients and showed an inverse correlation with nerve conduction velocity suggesting that ox- LDL/VLDL may be a contributing factor in the pathogenesis of diabetic neuropathy. The serum peroxynitrite concentration was significantly increased in our patients suggesting the possible implication of reactive nitrogen species in the pathogenesis of diabetic polyneuropathy via complex metabolic and vascular effects.