Objective To investigate the influence of melatonin and vitamin E on oxidative stress in kidneys of the early stage of diabetic rats.Methods Sparague-Dawley rats were randomly divided into normal control(NC) group,diabetic control(DMC) group,diabetic group treated with melatonin(DM+M) and diabetic group treated with vitamin E(DM+E).Melatonin(2 mg·kg-1) or vitamin E(100 mg·kg-1) was given intraperitoneally for 14 successive days after induction of diabetes with alloxan(200 mg·kg intraperitoneally).Blood glucose,blood lipid,kidney weight/body weight ratio,blood uria nitrogen,serum creatinine and malondialdehyde(MDA),nitric oxide(NO),the activity of antioxidant enzymes including superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px) in the renal tissue were measured.Results Compared with NC group,DMC group showed a significant increase of blood glucose,total cholesterol,triglyceride,kidney weight/body weight ratio,blood urea nitrogen and serum creatinine.The contents of MDA and NO and the activity of GSH-Px were increased significantly,while the activity of SOD decreased significantly in renal tissues of DMC group than those in NC group.Compared with DMC group,melatonin and vitamin E caused a significant decrease of total cholesterol and triglyceride,but no significant difference of blood glucose and serum creatinine.Elevated kidney weight,kidney/body weight ratio,blood uria nitrogen were reduced by melatonin,but not in DM+E group.Furthermore,in kidney tissue of diabetic rats treated with melatonin or vitamin E,SOD activity was increased significantly,and the increased GSH-Px activity reversed,while MDA and NO decreased significantly.The antioxidant effects of melatonin were greater than that of vitamin E.Conclusion These results confirm the role of oxidative stress in the development of early diabetic nephropathy and point to the possible antioxidative mechanism of the nephroprotective action of melatonin.Moreover,melatonin may be a more powerful antioxidant than vitamin E.