The present study was conducted to evaluate the response of kidneys in Wistar rats following long-term exposure to Al₂O₃ nanomaterials (NMs). To achieve this objective, Al₂O₃ of three different sizes (30 nm, 40 nm and bulk) was orally administered for 28 days to 9 groups of 10 Wistar rats each at the dose of 500, 1000 and 2000 mg/kg/rat. A tenth group of 10 rats received distilled water and served as control. After 28 days of exposure the animals were sacrificed and the serum was collected and tested for the activity levels of creatinine and urea following standard methods. Induction of oxidative stress was also investigated by assessing thiobarbituric acid reactive substances (TBARS) (MDA), protein carbonyl, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities. A histopathological evaluation was also performed to determine the extent of kidney damage. The results showed that both serum creatinine and serum urea levels increased significantly in the treated rats compared to control animals. The increase was found to be more in Al₂O₃-30 nm treated rats followed by Al₂O₃-40 nm and Al₂O₃-bulk treated rats in a dose-dependent manner. Further administration of Al₂O₃ significantly increased the activities of TBARS, protein carbonyl, catalase and decreased the activities of GSH and SOD in a dose-dependent manner in the kidney of rats compared with the control group. Histopathological evaluation showed significant morphological alterations in kidney tissues of treated rats in accordance with biochemical parameters. Taken together, the results of this study demonstrate that Al₂O₃ is nephrotoxic and its toxicity may be mediated through oxidative stress. Further, the results suggest that prolonged oral exposure to Al₂O₃ NMs has the potential to cause biochemical and histological alterations in kidney of rats at high concentration.