Regular exercise has beneficial effects on cerebrovascular diseases; however, its biochemical mechanisms are not fully known. The purpose of this study was to determine antioxidant enzyme activities and lipid peroxidation of both hippocampi after applying exercise followed by occluding one common carotid. Wistar rats were divided into four groups of control, exercise, hypoperfusion and exercise-hypoperfusion (exe-hypo). In the exercise and exe-hypo groups, the rats were forced to run on a treadmill for 1 h a day for 2 months. The right common carotid of the animals in the (exe-hypo) group was occluded after the cessation of exercise. Surgery without occlusion of the carotid was applied on the control (without exercise) and exercise groups. All animals were sacrificed 1 and 24 h after surgery. The levels of malondialdehyde (MDA) and antioxidant enzyme activities in the hippocampi were measured. A significant interaction was observed between the exercise and hypoperfusion in both hippocampi (p<0.05). In comparison with the control group, there was significant elevation of catalase activity in the right and left hippocampus of the hypo group at 24 h (p<0.0001). Regarding the differences between the hemispheres, there was a significant increase in MDA and decrease in catalase activity in the left hippocampus in hypoperfusion group, but the exercise in the exe-hypo group succeeded in abolishing these alterations which were caused by hypoperfusion, This study shows that exercise pre-conditioning prevents some alterations in brain oxidant-antioxidant status which are induced by cerebral hypoperfusion. Further studies are needed in order to clarify the mechanism of exercise.