Although regular physical exercise is beneficial to the body, it is well known that exhaustive exercise causes oxidative stress in muscle. Recent studies suggest that regular moderate physical exercise has the beneficial effects on brain. There is a little information regarding whether or not exercise could generate oxidative stress in the brain and the findings are conflicting. The aim of this study was to investigate the effects of acute and chronic exercise on thiobarbituric acid reactive substances, as an indicator of lipid peroxidation, in the hippocampus, which has a high concentration of glucocorticoid receptors, and prefrontal cortex and striatum, which have high dopamine content. Additionally we examined antioxidant enzyme activities, superoxide dismutase and glutathione peroxidase and nitrite-nitrate levels to assess the effects of reactive oxygen and nitrogen species. In this study it was shown that acute treadmill exercise at different strengths did not cause oxidative stress in prefrontal cortex, striatum and hypocampus regions of the brain. Regular treadmill exercise performed at different strengths was shown not to cause oxidative stress in prefrontal cortex, striatum and hippocampus regions of brain. As a result, we propose that acute and chronic exercise do not cause oxidant stress in prefrontal cortex, striatum and hippocampus and chronic exercise has a favorable effect on hippocampus, possibly by decreasing superoxide radical formation. (c) 2009 Published by Elsevier Ireland Ltd.