Oxidant stress and a reduction in antioxidant status, including reduced plasma and tissue ascorbic acid content, occur in diabetic patients and experimental models of diabetes. In this study, the effects of treatment of streptozotocin diabetic rats for 2 mo with vitamin C (10 g/kg body wt/d) or dietary vitamin E (200 mg/kg body wt/d) in the drinking water on urinary albumin excretion, glomerular transforming growth factor (TGF)-beta content, and glomerular size were examined. Treatment of diabetic rats with vitamin C or E had no effect on blood glucose levels compared with that in untreated diabetics (453 +/- 28 g/dl +/- SEM). Body weight, BP, and creatinine clearance rates were not significantly different among the study groups. Kidney weight was significantly higher in all of the diabetic groups compared with age-matched control rats. Treatment with vitamin C, but not vitamin E, significantly reduced kidney weight compared with that in untreated diabetic rats. Immunohistochemical staining for TGF-beta was 2.5-fold higher in glomeruli of cortical sections from untreated diabetic rats versus control rats. Treatment with vitamin C or E prevented the increase in glomerular TGF-beta immunoreactivity. Glomerular volume was also significantly increased (twofold) in kidneys of untreated diabetic rats compared with control rats, as assessed by light microscopy. Treatment with vitamin C prevented and treatment with vitamin E reduced the increase in glomerular volume. Treatment with vitamin C also prevented the sevenfold increase in albumin clearance otherwise seen in untreated diabetic rats. By contrast, treatment with vitamin E had no effect on albumin clearance despite reductions in glomerular size and TGF-beta. Renal cortical vitamin E and plasma, but not renal cortical vitamin C, were reduced in diabetic rats versus control rats. Supplementation of diabetic rats with vitamin C markedly increased plasma and renal cortical vitamin C content to values greater than those in control rats. Supplementation with vitamin E increased renal cortical vitamin E content by 50% compared with values in control rats and also increased plasma and renal cortical vitamin C. These results support the potential utility of antioxidant treatment for the prevention of renal injury in diabetes.