Objective  To investigate the mechanism of neuronal apoptosis induced by cyclooxygenase-2 (COX-2) after cerebral ischemia/reperfusion（CI/R）injury in rats.  Methods  Totally 45 male SD rats were divided into 3 groups by random number method, sham operation group (sham), model group (CI/R), COX-2 inhibitor group (NS-398). Blocking the middle cerebral artery to create a model, at the beginning of ischemia, NS-398 group was intraperitoneally injected with NS-398（20 mg/kg）, while sham group and CI/R group were injected with the same amount of DMSO. Rats were performed for neurofunctional scores after 2 hours ischemia. After 24 hours reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to detect the infarct volume of rats. Meanwhile, cerebral tissue from penumbra area of frontal parietal cortex on ischemic side was taken, Nissl staining and TUNEL method were used to detect neuronal damage and apoptosis respectively, and finally Western blotting was used to detect the expression levels of COX-2,Bcl-2 and Bax proteins.  Results  The neurofunctional scores of rats, cerebral infarction volume, apoptosis index, the expressions of COX-2 and Bax in CI/R group were higher than those in the sham group (P<0.05)，the expression level of Bcl-2 and the number of neurons were lower than those in the sham group (P <0.05); The neurofunctional scores of rats, cerebral infarction volume, apoptosis index, the expression levels of COX-2 and Bax in NS-398 group were lower than those in CI/R group (P<0.05), the expression level of Bcl-2 and the number of neurons were higher than those in CI/R group (P<0.05).  Conclusion  COX-2 may promote neuronal apoptosis after cerebral ischemia/reperfusion injury by regulating the expressions of Bcl-2 and Bax.