The present study was performed to investigate the effects of chronic administration of daidzein on lipid peroxidation and glutathione concentration in the livers and brains of rats. Male Sprague-Dawley rats were divided into two groups, one of which was fed a normal diet and the other a vitamin E-free diet. Each of these groups was divided further into three subgroups and treated either with vehicle or with daidzein administered orally at either 2 or 20 mg/day for 4 weeks. The concentrations of α-tocopherol in the serum and the brain increased following daidzein treatment, and these increases were significantly greater in rats maintained on a vitamin E-free diet. Daidzein significantly decreased the concentration of malondialdehyde in the organs, and this decrease was more pronounced in vitamin E-deprived rats than in those maintained on a normal diet. Although the liver glutathione concentration was not affected, daidzein treatment (20 mg/day) decreased the glutathione concentration in the brain significantly and to a similar extent in vitamin E-deprived rats and those fed normal diet. In addition the daidzein metabolite, equol, severely decreased the ratio of GSH and GSSG in primary cortical neuron cells exposed to it. Collectively, these results suggest that daidzein may act not only as an antioxidant, but also a prooxidant in brain rats, this should be in the brains of rats.