Objective: To explore the characteristic of the expression of COX-2 protein in different intervals following permanent focal cerebral ischemia in rats. Methods: A model of the middle cerebral artery occlusion (MCAO) in rats was performed with the intraluminal filament occlusion. The rats brains were cut in the coronal planes at the levels of the caudoputamen as the templates. The immunohistochemistry staining was used to facilitate the observation of the distributions and quantities of COX-2 protein in the brain tissues following the sham operation and the permanent MCAO for 1 h, 4 h, 12 h, 24 h and 48 h respectively. Results: There were no immunochemistry positive staining among the control group, the sham operation group, and the beginning ischemic group with MCAO for 1 h and 4 h. However, a significant increase in COX-2 immunostaining was detected 12 h after MCAO [(46 ± 19)/mm2]. It was most marked 24 h [(70 ± 14)/mm2], by 48 h after MCAO the positive staining cells gradually decreased [(41 ± 13)/mm2]. The difference among those groups was significant (P < 0.01). The immunochemistry positive staining only occurred in the neurons and vascular endothelials in the upper frontoparietal cortices and cingulate gyri, whereas the gliocytes did not show positive staining. Conclusion: The induction of COX-2 protein was evident in neurons and vascular endothelials at the ischemic penumbra, and the characteristics of the delayed expression indicated that it might involve in the mechanism of delayed neuronal death.