Severe hypoxia induces oxidative stress, which can lead to brain injury. In this study, we wanted to determine whether intermittent hypobaric hypoxia induces oxidative stress in the brain. In adult rats exposed to 380 mmHg in a hypobaric chamber for 3 h/day for 6 days, we determined the levels of malondialdehyde and nitric oxide derivatives in the brain, which indicated that there was no oxidative stress. The levels of N-acetylaspartate indicated that there was no neuronal loss or mitochondrial dysfunction and finally because apoptotic proteins such as caspase-3 and nuclear factor-kappa B (NF-κB) were not activated, apoptosis was probably not induced. The increase in the expression of erythropoietin (EPO) in the brain of rats exposed to hypoxia confirms the efficacy of the method used to induce hypoxia in the brain. Because EPO have antioxidant effects on the brain, the results suggest that intermittent hypoxia can increase the antioxidant capacity of the brain. This effect of intermittent hypoxia was studied using the systemic administration of kainate, as a model of brain oxidative stress. Kainate treatment induces oxidative stress in the brain, which is measured by an increase in lipid peroxidation and nitric oxide. Furthermore, in rats treated with kainate, both caspase-3 and NF-κB activity increased. However, in rats previously exposed to intermittent hypobaric hypoxia, 3 h per day for 6 days, the effect of kainate treatment resulted in the reduction of both oxidative stress and apoptotic activity. This study demonstrates that intermittent hypobaric hypoxia can increase brain antioxidant capacity in rats and induces neuroprotection in kainate-induced oxidative injury.