Vitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca2+-ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca2+-ATPase activity and calcium levels in kidney of streptozotocin (STZ)-induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg kg(-1) i.p.). After diabetes was verified, diabetic and age-matched control rats were untreated or treated with vitamin E (400-500 IU kg(-1) day(-1), orally) for 10 weeks. Ca2+-ATPase activity and lipid peroxidation (NIDA) were determined spectrophotometrically. Blood glucose levels increased approximately five-fold (> 500 mg dl(-1)) in untreated-diabetic rats but decreased to 340 +/- 27 mg dl(-1) in the vitamin E treated-diabetic croup. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment 2 markedly inhibited NIDA levels in both control and diabetic animals. Ca2+-ATPase activity was 0.483 +/- 0.008 U l(-1) in the control group and significantly increased to 0.754 +/- 0.010 Ul(-1) in the STZ-diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes-induced increase in Ca2+-ATPase activity (0.307 +/- 0.025 U l(-1), p < 0.001) and also reduced the enzyme activity in normal control rats. STZ-diabetes resulted in approximately two-fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes. Copyright (C) 2003 John Wiley Sons, Ltd.