The purpose of this study is to investigate  the adverse effects of repaglinide. Twenty  of  male  albino  rats  were  randomly  divided   into  four groups (five of each): (i) Control, (ii) Vitamin E (100 mg/kg b.wt) administered orally, (iii) Repaglinide (0.09mg/kg b.wt) administered orally, and  (iv)  Vitamin E plus repaglinide were administered orally at the same doses. Treatment with Vitamin E and /or repaglinide were continued for 2 successive weeks. At the end of experiment, serum samples were obtained for some biochemical analysis including:  catalase (CAT), superoxidase dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). Kidney and liver were taken for histopathological examination. The obtained results showed a significant decrease in the serum level of CAT, SOD, GPx and a significant increase in the level of MDA in repaglinide group compared to the control group. Meanwhile, the group treated with vitamin E plus repaglinide revealed an improvement in the values of antioxidant enzymes compared to rats administered repaglinide group. Liver sections showed a focal co-agulative necrosis with cell aggregation  and kidney sections revealed a necrotic glomeruli with destructed  hemorrhagic renal tubules in the rats treated with repaglinide. However, rats treated with both vitamin E plus repaglinide illustrated a noticed recovery of liver and kidney tissues. In conclusion, administration of vitamin E can be recommended to overcome side effects associated with repaglinide by its protective antioxidant activity.