This study was conducted to evaluate the possible protective effect of vitamin E (100 mg/kg) on Pantoprazole adverse effects (3.6 mg/kg) based on its antioxidant scavenging capacity and histopathological examination. Eighty rats were used as 4 separate groups, 20 rats per each. Group (I) is a control group received saline; Group (II) is a vitamin E group received Vit. E (100mg/kg BW,P.O once daily) for 21 successive days, Group (III) is a pantoprazole group received pantoprazole (3.6 mg/kg BW,P.O once daily) for 21 successive days, Group (IV) is pantoprazole and Vit. E group received pantoprazole and Vit. E once daily for 21 successive days. The adverse effects of pantoprazole and the protective effects of vitamin E were assessed in blood at day one, day 7, day 14 and day 21 after drug withdrawal and in tissue samples at 7^th and 14^th days after drug withdrawal. Our results show a significant increase in serum antioxidant enzymes (CAT- SOD- GPX) and a significant reduction in lipid peroxidation (MDA) in vitamin E treated group, In addition to show reduction in liver fatty changes with decrease in degenerative changes in hepatocytes induced after giving pantoprazole. Also, degenerative changes in renal tubular epithelium caused after giving pantoprazole were minimized by vit. E. For these reasons Vitamin E should be advised to be used concurrently with Pantoprazole to reduce its adverse effects.