Although Cyclooxygenase-2 (COX-2) is essential for mouse ovulation, fertilization, implantation and decidualization, the regulation and function of COX-2 in rat reproduction are still unknown. This study was designed to examine the action of COX-2 in rat ovulation, implantation and decidualization by using two specific inhibitors of COX-2 (nimesulide and niflumic acid). Compared to control, either nimesulide or niflumic acid significantly inhibited the ovulation in the superovulated rats. Although nimesulide had no obvious effects on the number of implantation sites and the vascular permeability, the expression of PPARdelta, HB-EGF and vimentin proteins was down-regulated in the nimesulide-treated groups. COX-1 protein was upregulated by nimesulide treatment. Nimesulide also had an inhibitory effect on decidualization during early pregnancy and under artificial decidualization. Moreover, nimesulide caused the increase of the gestation period and the reduction of litter size and birth weight compared to controls. Based on our data, rat implantation and decidualization were delayed by nimesulide treatment, resulting in the reduction of litter size and birth weight and the prolongation of gestational length, suggesting that COX-2 plays an important role in implantation and decidualization.