Chronic exposure to psychological stress in humans and restraint stress in experimental animals results in increased oxidative stress and resultant tissue damage. To study the contribution of stress hormones towards stress-induced oxidative processes in the brain, we investigated the response of important free-radical scavenging enzymes toward chronic administration of two doses of corticosterone (low dose: 10 mg/kg/day, high dose: 40 mg/kg/day) in rodents. After a 21-day experimental period, a significant decline in both superoxide dismutase and catalase was observed in both stressed and stress hormone-treated animals. The brain levels of glutathione as well as the activities of glutathione-S-transferase and glutathione reductase were also significantly decreased, while lipid peroxidation levels were significantly increased in comparison to controls. A direct pro-oxidant effect of stress hormones in the brain during physical and psychological stress was observed, indicating important implications for oxidative stress as a major pathological mechanism during chronic stress and a consequent target option for anti-stress therapeutic interventions.