Raloxifene (RAL) is a selective estrogen receptor modulator (SERM), presenting tissue-specific agonist activity. The aim of this study was to examine whether RAL has an estrogenic effect on carrageenan-induced acute inflammation. Adult female rats were ovariectomized seven weeks before edema or pleurisy to deplete circulating estrogens. Edema formation and selected inflammatory markers in inflamed paw tissue were measured in intact (SHAM) and ovariectomized (OVX) rats. Groups of OVX rats were treated with RAL (1, 3 or 10 mg/kg) or 17-estradiol (E₂, 25 µg/kg) and these treatments began 2 days after surgery and continued until carrageenan paw edema or pleurisy. Ovariectomy amplifies the inflammation and we found that RAL, as well as E₂, attenuates inflammation and tissue damage associated with paw edema and pleurisy. In treated rats there is a decrease in edema development and formation, and in polymorphonuclear cell infiltration and migration, as shown by myeloperoxidase measurement and cell counting. RAL and E₂ treatments decrease COX-2 and iNOS expression in inflamed areas, and counteract the inhibition of PPAR- expression caused by ovariectomy, restoring this receptor protein expression to SHAM levels and identifying a possible PPAR-dependent anti-inflammatory effect of these drugs. Moreover, RAL and E₂ increase cytoprotective hsp72 protein expression, which seems to be closely associated with the remission of the inflammatory reaction. In addition, we confirm the anti-inflammatory effect of RAL in male rats using a single administration of RAL or E₂.