The goal of the current work was to investigate whether vitamin E had any protective effects against nicotine-induced nephrotoxicity in rats. Thirty mature male rats, weighing 200–250 g, were placed into 3 groups at random. Rats in the control group obtained saline, whereas Nicotine group: rats supplemented with nicotine (0.8 mg/kg/day; s.c.). Vitamin E+ nicotine group: rats were co-administered vitamin E (100 mg/kg/day; orally) followed by nicotine. The experiment duration was 30 days. Exposure of rats to nicotine resulted in significant rise in serum urea and creatinine levels, serum total oxidant status, tumor necrosis Factor-α and kidney tissue nitric oxide, malondialdehyde and caspase-3 levels. Otherwise, significant decrease in total antioxidant capacity. Moreover, the kidney histopathology investigation revealed significant damage. In addition to significant decrease in rats' weight and increase in relative kidney weight. On the other hand, the supplementation of Vitamin E altered the biochemical parameters and the histopathological findings. The results demonstrated that supplementation of Vitamin E protects against nicotine- induced kidney oxidative stress, inflammation and apoptosis.