In this study, the authors aimed to investigate the role of oxidative stress on the hepatic damage caused by methotrexate (MTX) and the possible protective effects of beta-carotene against this damage. The rats were divided into four groups as control, MTX (20 mg/kg ip), beta-carotene (10 mg/kg/day ip) | MTX, and beta-carotene. Histopathologic alterations were evaluated for defining the liver damage. The tissue, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GP-x) contents and serum aspartate aminotransferase (AST) and alanine aminotranferase (ALT) activities were also examined. Histopathologic damage for each group score findings have been determined as control: 0.66 +/- 0.33; MTX: 7.0 +/- 0.68; beta-carotene | MTX: 3.3 +/- 0.42; and beta-carotene: 0.5 +/- 0.3. In the MTX-treated group, MDA, AST, and ALT values were increased, while SOD and GP-x values were decreased compared with the control group. In the beta-carotene + MTX-treated group, AST and ALT values significantly decreased, while all other parameters were similar to the control group. This study shows that beta-carotene has a protective effect on MTX-induced oxidative hepatic damage. Consequently, it seems that an antioxidant agents like beta-carotene may be useful in decreasing the side effects of chemotherapy.