Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Edaravone (EDA, 3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent free radical scavenger. In this study, the aim was to investigate the effects of EDA on VPA-induced hepatic damage. Male Sprague Dawley rats were divided into four groups. Group I was control animals. Group II was control rats given valproic acid (500 mg kg(-1) day(-1)) for seven days. Group III was given only EDA (30 mg kg-1 day-1) for seven days. Group IV was given VPA+EDA (at the same dose and in the same time). EDA and VPA were administered intraperitoneally. On the 8th day of the experiment, blood samples and liver tissue were taken. Serum aspartate and alanine aminotransferase, alkaline phosphatase and bilirubin levels, liver myeloperoxidase, xanthine oxidase, adenosine deaminase, Na+/K(+)ATPase, sorbitol dehydrogenase, glutamate dehydrogenase, DT-diaphorase, arginase and thromboplastic activities, lipid peroxidation, protein carbonyl levels were increased whereas paraoxonase and biotinidase activities and glutathione levels were decreased in the VPA group. Application of EDA with VPA protected against VPA-induced effects. These results demonstrated that administration of EDA is potentially beneficial to reduce hepatic damage in VPA-induced hepatotoxicity, probably by decreasing oxidative stress.