Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis. It is clinically well-defined and represents one manifestation of the atopic state, along with asthma and/or allergic rhinitis. Based on many immunological facts appear in atopic dermatitis patients, among them, the T lymphocytes immune-activity and the imbalanced cytokine production by the inflammatory cells. It is likely that activated lymphocyte and Interferon-gamma( IFN-γ), Interleukin 4(IL-4) and Interleukin 10(IL-10) not only of major importance in pathogenesis of atopic dermatitis but also they could be important in outcome prediction and possibly as therapeutic targets. Fifty atopic dermatitis patients (30 female and 20 male) were giving two types of treatment and 43/50 were re-analyzed after one month of treatment with tacrolimus or topical and systemic steroids. These patients who attended to private clinic during the period extended from May 2008 to September 2008. Patients were selected randomly and the mean age of patients 26±11 years and range from 6-45 years, most frequent age group was in second decade group(30%).Most of the patients (74%) were presented with high disease activity. Patients were diagnosed as an atopic dermatitis according the diagnostic criteria of Hanifin and Rajika (Hanifin and Rajika 1980). Specimens (Blood and Urine) were collected from them following the guide-lines of WHO(1995). Skin swabs was done for all patients. Skin biopsies were taken from ten patients before and after treatment. Blood sample was taken from each subject and divided into two parts, the heparinized blood used for lymphocyte separation, smears were prepared, fixed on charge slides, wrapped and kept at -20 Cº until assayed. While un-heparinized blood allowed clotting, serum collected and kept at -20 Cº until assayed. Immunocytochemical and immunohistochemical staining techniques were used to detect CCR3 and CCR5 expression whereas the serum concentration of IFN-γ, urine and serum concentration of IL4 , IL-10 and total IgE were determined using Enzyme Linked Immuno -Sorbant Assay(ELISA). Immunocytochemistery staining and Immunohistochemical staining of peripheral blood lymphocytes (PBLs) and epidermal cell expression of CCR3 and CCR5 in AD skin lesions revealed highly statistical significant differences with lower mean percentage of expression in patients after treatment with that of the pre-treatment results and there was no statistical significant differences of these activation markers between the treatment with topical steroid and topical tacrolimus. The expression of chemokine receptor (CCR-3) revealed lower mean percentage of expression on PBLs and epidermal cell as compared with the chemokine receptor CCR-5 of Th1. Thus, we can depend on the PBLs and epidermal cell expression of CCR3 and CCR5 as a laboratory parameter to define the degree of general disease activity (valid biomarker) for AD patients and using of their blockers in treatment of patients especially those suffering from recurrent active disease. The sera of patients group revealed a statistically significant increase in the concentration of IFN-γ, IL-4 and IL-10 before treatment when compared with that of the same patients after treatment and also there was no statistically significant differences between two treatments.Serum IFN-γ have a quite consistence and strong positive correlations with most of the clinical and laboratory disease activity indices, and also have strong positive correlation with the PBLs and epidermal cell expression of CCR3 and CCR5. Thus, we can depend on the serum IFN-γ concentration as a laboratory parameter to define the degree of general disease activity (valid biomarker) for chronic AD patients and using of its blocker in treatment of patients especially those suffering from recurrent active disease. The urine of patients group revealed a statistically significant difference with higher concentration of IL-10 in urine of patients before treatment when compared with that of the same patients after treatment whereas there was no statistically significant difference of urine concentration of IL-4 before and after treatment. This mean the IL-10 concentration in urine play a role in evaluation the activity of disease before and after treatment. High concentration of total Immunoglobulin E (IgE) was detected in 43 (74%) patients and most patients have high level of eosinophil count at time of diagnosis and statistically significant difference before and after treatment. In conclusion; there was statistically significant difference of all these markers mentioned above before and after treatment with both topical steroid and topical tacrolimus thus we can depend on all these markers to evaluate the activity of the AD disease(valid biomarkers), whereas, no statistically significant difference of these markers when we compare the two treatments, this means the new immuno-modulator tacrolimus represent a safer class of drugs that alter the local immune response in a more targeted fashion than do older steroid and clear the rash with few side effects.