Objectives: The aim of this study is to investigate the effect of eicosapentaenoic acid combined with vitamin C in comparison with the pure form of eicosapentaenoic acid on the serum concentration of malondialdehyde, erythrocyte activity of superoxide dismutase, glutathione peroxidase, and the serum level of total antioxidant capacity in patients with type 2 diabetes. Methods: Eighty one male diabetic patients, aged 33-63 years, were randomly assigned to one of 4 groups. The subjects consumed 500 mg/d pure eicosapentaenoic acid, 200 mg/d vitamin C, 500 mg eicosapentaenoic acid and 200 mg/d vitamin C or placebo depending on their groups. In fasting blood samples, superoxide dismutase and glutathione peroxidase activities were determined via the enzymatic method (Randox kit) and the serum total antioxidant capacity, malondialdehyde and vitamin C concentrations were estimated by colorimetric methods. Results: Administration of pure eicosapentaenoic acid in diabetic patients increased superoxide dismutase by 4%, glutathione peroxidase 53%, total antioxidant capacity 36% and decreased malondialdehyde significantly by 25%. Prescription of eicosapentaenoic acid combined with vitamin C demonstrated a significant increment for superoxide dismutase activity by 3% and for glutathione peroxidase activity by 52% during the study, but no significant change was seen for total antioxidant capacity and malondialdehyde, respectively. There was a significant decrease in FBS and HbA1c following prescription of eicosapentaenoic acid with/without vitamin C along the study, although these changes were not significant between the study groups. Conclusion: It is concluded that prescription of eicosapentaenoic acid in the pure form reduces oxidative stress in type 2 diabetic patients; albeit, it does not alleviate hyperglycemia. Combination of vitamin C and eicosapentaenoic acid does not improve antioxidant property of eicosapentaenoic acid.