The efficacy of hyperbaric oxygen (HBO) therapy for treatment of stroke remains to be validated in the laboratory. We report here that adult rats subjected to occlusion of the middle cerebral artery and subsequently exposed to HBO (3 atm, 2 x 90 min at a 24-h intervals; animals terminated shortly after the second treatment) or hyperbaric pressure (HBP; 3 atm, 2 x 90 min at a 24-h interval; animals terminated shortly after the second treatment) immediately after the ischemia or after a 60-min delay generally displayed recovery from motor deficits at 2.5 and 24 h of reperfusion, as well as a reduction in cerebral infarction at 24 h of reperfusion compared to ischemic animals subjected to normal atmospheric pressure. While both HBO and HBP treatments promoted beneficial effects, HBO produced more consistent protection than HBP. Treatment with HBO immediately or 60 min after reperfusion equally produced significant attenuations of cerebral infarction and motor deficits. In contrast, protective effects of HBP treatment against ischemia were noted only when administered immediately after ischemia, which resulted in a significantly reduced infarction volume, but only produced a trend toward decreased behavioral deficits. The present results demonstrate that HBO and, to some extent, HBP reduced ischemic brain damage and behavioral dysfunctions.