Oxygen-derived free radicals have been implicated in the pathogenesis of doxorubicin-induced toxicities. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on doxorubicin-induced neuronal oxidative injury in rats. The rats were treated with CAPE (10 mumol/kg/day i.p.) or saline starting 2 days before a single dose of doxorubicin (20 mg/kg i.p.) or saline. Ten days after the first experiments, the brain was excised to analyze the activities of antioxidant enzymes and levels of malondialdehyde (MDA) and nitric oxide (NO). Doxorubicin alone resulted in higher MDA level in brain tissue than the other groups. The activity of catalase was higher in doxorubicin plus CAPE group than doxorubicin group. There were no significant differences in NO level, glutathione peroxidase (GSH-Px) and superoxide dismutase activities between the groups. There were negative correlations between GSH-Px activity and MDA level in both doxorubicin and doxorubicin plus CAPE groups. It can be concluded that doxorubicin induced oxidant injury can be prevented by CAPE treatment through its antioxidant properties in rat brain.