Background/aims: The tolerance of the liver is considerably low when an effective radiation (RTx) dose needs to be delivered in patients in whom either their liver or whole body area has to be irradiated. The aim of this study was to evaluate the possible protective effect of grape seed extract on liver toxicity induced by RTx in the rat liver. Methods: We used four groups, each consisting of 12 healthy male Wistar rats. RTx-grape seed extract group: rats were given grape seed extract (100 mg/kg) orally for seven days, following 8 Gy whole body irradiation, and grape seed extract was maintained for four days. RTx group: the same protocol was applied in this group; however, they received distilled water instead of grape seed extract. Grape seed extract group: only grape seed extract solution was administered for 11 consecutive days in the same fashion. Control group: only distilled water (orally) was administered in a similar manner. The level of malondialdehyde, an end product of lipid peroxidation, and the activities of superoxide dismutase and catalase, two important endogenous antioxidants, were evaluated in tissue homogenates. Results: Grape seed extract was seen to protect the cellular membrane from oxidative damage and consequently from protein and lipid oxidation. In the RTx group, malondialdehyde levels were extremely higher than those of the grape seed extract-RTx group (p<0.001). Grape seed extract administration moderately reserved the malondialdehyde levels. RTx therapy decreased superoxide dismutase and catalase activities in the liver homogenates (p<0.001), and these alterations were significantly reversed by grape seed extract treatment (p<0.001). There were no differences between the grape seed extract-RTx, grape seed extract and control groups with regard to antioxidant activity (p>0.05). Conclusions: The levels of antioxidant parameters on RTx-induced liver toxicity were restored to control values with grape seed extract therapy. Grape seed extract may be promising as a therapeutic option in RTx-induced oxidative stress in the rat liver.