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To investigate the underlying mechanism of the protection on cerebral ischemia of o2adrenergic agonist clonidine.The cerebral ischemia rat model was made by right middle cerebral artery occlusion for 2 h and reperfusion for 4 h.The Sprague Dawley rats were randomly divided into the shamoperative group, the cerebral ischemia model group, the clonidine group, the yohimbine + clonidine group and the yohimbine group.The results shown that neurological deficit scores of rats pretreated with clonidine before the ischemia were better than the shamoperative group.Clonidine group had significantly reduced brain infarct volumes.Clonidine decreased the expression of phosphoNMDAR2B and increased the expression of phosphoNMDAR1 and NMDAR2A.Therefore, clonidine significantly alleviated cerebral ischemia / reperfusion injury.The mechanism may be related to the regulation of phosphoNMDAR2B, phosphoNMDAR1 and NMDAR2A during cerebral ischemia/reperfusion.