It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)-induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM-induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values and histological evaluation. Twenty-one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for I day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor-driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH-Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media-induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system. Copyright (c) 2009 John Wiley & Sons, Ltd.