Diabetes mellitus is a chronic syndrome affecting carbohydrate, fat, protein and nucleic acid metabolism. The current study was undertaken to elucidate the possible role of vitamin E and alpha lipoic acid in combination as an antioxidant and a biological membrane stabilizer in the protection against early complication of diabetes. Administration of alloxan (125 mg/kg wt, i.p.) to rats resulted in hyperglycemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia, increase in plasma levels of urea, blood urea nitrogen (BUN), creatinine, uric acid as well as pancreatic thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) content of both liver and retina. These changes were accompanied with significant decrease in plasma total protein, tumor necrosis factor α (TNFα), hepatic catalase activity (CAT), and TBARS level of both liver and retina as compared to control group. However, plasma levels of calcium ions (Ca+2) and nitric oxide (NO) as well as pancreatic GSH content were not changed. On the other hand, the daily treatment of the diabetic rats with antioxidant mixture attained a reduction in plasma levels of glucose, cholesterol, triglycerides, total lipids, urea, BUN, creatinine, uric acid, TNFα, pancreatic TBARS level as well as GSH content of both liver and retina. In contrast, the daily treatment caused an increase in plasma levels of insulin, total proteins, hepatic CAT activity and pancreatic GSH content as compared to diabetic rats. However, plasma levels of Ca+2 and NO as well as TBARS content of both liver and retina were not affected. In conclusion, it is obvious from the present study results that early stage (two weeks) of diabetes induce deteriorate changes in carbohydrate, lipid, protein and nucleic acid metabolism accompanied with increasing of oxidative stress in pancreas as compared to both of liver and retina. Moreover, the data of present study indicated the effective role of vitamin E and alpha lipoic acid combination in combating the oxidative stress via its improvement to metabolism of carbohydrates, lipids, proteins and nucleic acids in addition to its free radical-scavenging and antioxidant properties.