Cerebral ischemia leads to neuronal damage in the hippocampus and cognitive decline. Reactive oxygen species play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Deprenyl, an irreversible monoamine-oxidase B inhibitor, has antioxidant and neuroprotective effects against reactive oxygen species. In the present study, the effect of deprenyl on spatial memory impairment, oxidative stress and apoptotic neuronal cell death following transient cerebral ischemia in rats was investigated. Transient ischemia was induced by occlusion of left common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 1 mg/kg deprenyl (n = 24) or equal volume of saline (n = 24) for 14 days before the experiment. Deprenyl treatment attenuated spatial memory deficits following ischemia-reperfusion as measured by the Morris water maze task. Deprenyl treatment elicited a significant decrease in lipid peroxidation and increase in superoxide dismutase activities in ischemic rat brains. The number of TUNEL-positive cells decreased significantly in deprenyl-treated group when compared with the control group. The results show that deprenyl reduces the ischemia-induced oxidative stress and thus prevents spatial memory deficits and apoptotic neuronal cell death when it is administered before ischemia-reperfusion. © 2008 by The Chinese Physiological Society.