Recent studies suggest that intermittent and prolonged normobaric hyperoxia results in ischemic tolerance to reduce ischemia brain injury. In this research attempts were made to see the changes in antioxidant enzyme activities following prolonged and intermittent normobaric hyperoxia preconditioning. Rats were divided into four experimental groups, each of 21 animals. The first two were exposed to 95% inspired normobaric hyperoxia for 4 h/day for 6 consecutive days (intermittent normobaric hyperoxia) or for 24 h continuous (prolonged normobaric hyperoxia). The second two groups acted as controls, and were exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion-operated, sham-operated (without middle cerebral artery occlusion), and intact (without any surgery) subgroups. After 24 h, middle cerebral artery occlusion-operated subgroups were subjected to 60 min of right middle cerebral artery occlusion. After 24 h reperfusion, neurologic deficit score, infarct volume were measured in middle cerebral artery occlusion-operated subgroups. Antioxidant enzyme activities were assessed in sham-operated and intact subgroups. Preconditioning with prolonged and intermittent normobaric hyperoxia decreased neurologic deficit score and infarct volume, and increased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, the intermittent and prolonged normobaric hyperoxia seems to partly exert their effects via increase antioxidant enzymes activities.