Hypoxia plays the major role in the pathophysiology of neuronal injury during focal cerebral ischemia. The purpose of this study was to examine the effect of early hyperbaric oxygen (HBO2) treatment on neuronal survival in the rat brain after middle cerebral artery occlusion and reperfusion (MCAO/R). MCAO/R caused signifi cant neuronal apoptosis, cerebral infarction, and neurological defi cits. HBO2 treatment performed at 3 h after reperfusion signifi cantly reduced the neurological defi cit score by 27%, the infarct area ratio by 44%, and number of apoptotic cells by 21% compared with the untreated control group. However, when the HBO2 treatment was performed 18 h after reperfusion, it had no protective effect on neuronal apoptosis or cerebral infarction after MCAO/R. Our results indicate that early HBO2 treatment enhances neuronal survival and reduces neurological defi cits of rats after cerebral ischemia, and that delayed treatment is ineffective. We conclude that the benefi cial effect of HBO2 therapy for brain injury after cerebral ischemia is time-dependent. Hypoxia plays the major role in the pathophysiology of neuronal injury during focal cerebral ischemia. The purpose of this study was to examine the effect of early hyperbaric oxygen (HBO2) treatment on neuronal survival in the rat brain after middle cerebral artery occlusion and reperfusion (MCAO/R). MCAO/R caused signifi cant neuronal apoptosis, cerebral infarction, and neurological defi cits. HBO2 treatment performed at 3 h after reperfusion signifi cantly reduced the neurological defi cit score by 27%, the infarct area ratio by 44%, and number of apoptotic cells by 21% compared with the untreated control group. However, when the HBO2 treatment was performed 18 h after reperfusion, it had no protective effect on neuronal apoptosis or cerebral infarction after MCAO/R. Our results indicate that early HBO2 treatment enhances neuronal survival and reduces neurological defi cits of rats after cerebral ischemia, and that delayed treatment is ineffective. We conclude that the benefi cial effect of HBO2 therapy for brain injury after cerebral ischemia is time-dependent.