Abstract: To investigate the neuroprotective effect and possible molecular mechanism of PNU-282987 on rats subjected to ischemia and reperfusion. In this study, middle cerebral artery occlusion/reperfusion(MCAO/R)in rats was used as the animal model. The 44 Sprague-Dawley(SD)rats were divided into 4 groups, sham group, model group, low-dose of PNU-282987(1. 2 mg/kg)and high-dose of PNU-282987(2. 4 mg/kg)treatment group. Y-maze test was tested for the learning and memory abilities of rats, and we also examined the brain infarct size, brain edema and neurological dysfunction in rats. Furthermore, HE staining was used to evaluate the neuronal injury and TUNEL assay was used to evaluate the neuronal apoptosis in the rat brain. The results revealed that the learning and memory abilities of rats in treatment group improved significantly, and treatment with PNU-282987 reduced brain infarct size, lessoned brain edema, lessened neurological dysfunction, ameliorated pathological injury and prevented neuronal apoptosis. The above results suggest that the underlying mechanism of PNU-282987 on improving learning and memory abilities of rats after cerebral ischemia and reperfusion may include the inhibition of neuronal apoptosis.