This study aimed to explore the effects of hyperbaric oxygen (HBO2) on blood-brain barrier (BBB) integrity in rats, when administered for one (at 2.5 ATA, 3 HBO2 sessions a day) and five days (at 2.5 ATA, 3 HBO2 sessions a day for the first two days, and twice a day for the last three days). Horseradish peroxidase (HRP) was used to evaluate the BBB permeability. Superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) levels were measured in the cerebral cortex and hippocampus regions. Frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in the cerebral cortex and hippocampus of rats subjected to HBO2. The accumulation of HRP reaction products in these brain regions was significantly higher than that of control animals (P<0.01). In animals that received HBO2, MDA levels (P<0.01 for 5 days) and GSH (p<0.05 for one day, and P<0.01 for five days) were decreased in the cerebral cortex, whereas SOD activities slightly increased in this region. In animals that received HBO2 significant decreases in MDA (P<0.05 for one day; P<0.01 for five days) and GSH (P<0.05 for five days) levels were observed in the hippocampus region, but SOD activities decreased in this region.