Both physical and intellectual activity may reduce the incidence of neurodegenerative disorders. There is evidence that environmental enrichment (EE) can induce profound behavioral, neurochemical and neuroanatomical changes, thus producing lasting improvements in memory and learning tasks. In this study we evaluated the anti-oxidative effects produced by EE in the hippocampus and the cerebral cortex of male and female rats. The animals had been reared in either EE or control conditions. The parameters studied were: thiobarbituric acid reactive substances (TBARS), protein oxidation, total radical antioxidant parameter, catalase, superoxide dismutase and superoxide anion activity. The results showed that our EE protocol reduced markers of oxidative stress in the hippocampus and in the cerebral cortex. Overall, the measures taken in the two cerebral regions revealed that EE rats showed higher values for antioxidant measures and lower values for oxidative stress parameters than control animals. More importantly, a consistent sex difference was found, indicating that in female rats the hippocampus and cerebral cortex are plastic brain regions receptive to external stimulation such as EE. Although EE males have higher levels for antioxidant capacity, catalase and SOD, it is likely that females do not need to activate all the antioxidant defenses since they have a greater capacity to assimilate external stimuli. This is suggested by the similarity of protein oxidation and TBARS levels in hippocampus in both sexes, and the even lower levels of protein oxidation and superoxide anion activity in the cerebral cortex in EE females.