Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Proteins and lipids are among the prime targets for oxidative stress. In the present study, the oxidative stress was evaluated in 55 diabetic patients and 40 healthy subjects by measuring the levels of protein oxidation, lipid peroxidation and some enzymatic and nonenzymatic antioxidants. The oxidative products of protein (PCG) and lipid peroxidation (MDA) and nitric oxide levels in plasma of NIDDM patients were significantly increased. However, the levels of enzymatic (GPx, SOD, catalase in RBC) and nonenzymatic (beta-carotene, retinol, vitamin C & E and uric acid) antioxidants of RBC showed a significant decrease in NIDDM patients compared to normal subjects. Serum protein analysis by polyacrylamide gel electrophoresis (PAGE) showed the significant difference in the ceruloplasmin, transferrin, albumin, retinal binding protein, etc. in diabetic patients compared to healthy controls. In conclusion, the results suggest that increased protein oxidation, lipid peroxidation and NO levels, decreases the levels of enzymatic and nonenzymatic antioxidants and playing a major role in diabetic complications.