BACKGROUND Aflatoxins are toxic metabolites produced by Aspergillus flavus and Aspergillus parasiticus and are classified as group I carcinogens by the International Agency for Research on Cancer (IARC). OBJECTIVE The purpose of this study was to investigate the possible preventive role of vitamin E (Vit E) on aflatoxin (AF) induced toxicity by using biochemical and histopathological approaches. METHODS Wistar-Albino rats were divided into 4 groups as follows: control group, Vit E group (Vit E was administered), AFB1 group (a single dose of AFB1 was administered), AF + Vit E group (AF and Vit E were administered). The effects of Vit E on AFB1 induced tissue toxicity were evaluated by using malondialdehyde (MDA), reduced glutathione (GSH) levels, antioxidant enzyme activities, and histopathological examination in tissues. RESULTS AF caused the oxidative stress by the increased MDA level and the reduced GSH level, glutathioneS-transferase (GST), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glucose-6-phosphate dehydrogenase (G6PD) activities in tissues. Plasma aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities, creatinine, and urea concentrations significantly increased; whereas, chloride, phosphorus, and magnesium concentrations were insignificantly affected. Plasma glucose, protein and sodium concentrations significantly decreased. Administration of AF caused hepatotoxicity, cardiotoxicity, and nephrotoxicity. As far as histopathological changes are concerned, a statistically significant difference was found in AFB1 group compared to the control group. Vit E considerably reduced plasma AST, ALT, ALP, LDH activities, and urea concentration and ameliorated the deleterious effects of AF on oxidative stress markers and pathological changes. CONCLUSIONS This data indicated that the natural antioxidant Vit E might have a protective effect against AF-induced toxicity and oxidative stress.