Objective To investigate the effect of hydromorphone on cerebral ischemia-reperfusion injury in rats．Methods Forty-five SD male rats were randomly divided into three groups：sham-operated group（Sham group）, cerebral ischemia-reperfusion group（I/R group）and hydromorphone group（HM group）．The animal models were constructed using the Zea-Longa modified line tethering method, and neurological function was evaluated by the Zea-Longa score after 24 h of reperfusion．TTC staining was used to detect the volume of cerebral infarction, hematoxylin-eosin（HE）and Nissl staining were used to observe the pathological changes of hippocampal neurons, and Tunel staining was used to observe apoptosis, Western blot, qPCR were used to detect apoptosis Bcl-2, Bcl-2-associated X protein（Bax）and cysteine protease（Caspase）-3 protein and mRNA expression．Results Compared with the I/R group, the HM group showed lower neurological function scores and cerebral infarct area（P<0.05）, smaller number of Tunel-positive cells（P<0.05）, less mRNA expression of Bax and Caspase-3 proteins and significantly higher expression of Bcl-2（P<0.05）．Conclusions Hydromorphone has neuroprotective effects and can reduce cerebral ischemia-reperfusion injury in rats．