Cyclooxygenase (COX) generates free radicals and it is important in inflammatory response. In this study, we observed the immunoreactivity in mice (ICR and C57BL/6 strain), rats and gerbils. In these animals, COX-2 immunoreactivity was mainly detected in pyramidal cells of the hippocampal CA2/3 region and in granule cells of the dentate gyrus. COX-2 immunoreactivity in the CA2/3 region was the highest in ICR mice, while in gerbils COX-2 immunoreactivity was the lowest; COX-2 immunoreactivity in the dentate gyrus was the highest in rats and the lowest in gerbils. The protein levels of COX-2 were similar to the immunohistochemical data. COX-2 mRNA transcript was the highest in the gerbil and the lowest in the rat. In brief, COX-2 protein, not mRNA, in the hippocampus is generally higher in mice (ICR and C57BL/6 strain) than rats and gerbils.