Previous studies have produced conflicting data on the contribution of the peroxisome proliferator-activated receptors (PPARs) to the inflammatory process. This study investigated the effects of several PPARalpha and PPARgamma subtype-specific agonists on the inflammation and hyperalgesia produced by intraplantar carrageenan injection in unanesthetized male Sprague-Dawley rats. Intraperitoneal administration of PPARalpha agonists reduced edema in parallel to their potencies determined in vitro. Perfluorooctanoic acid (PFOA) inhibited carrageenan-induced edema in a dose-dependent manner, and also reduced thermal hypersensitivity. Furthermore, PFOA produced much more robust effects when administered 0.5-24 hrs before carrageenan, as compared to when it was administered 1.5 hrs after carrageenan. Intraperitoneal administration of similar doses of the PPARgamma agonist rosiglitazone, but not the less potent agonist, troglitazone, reduced edema when administered before but not after carrageenan. We conclude that systemic administration of potent PPARalpha and PPARgamma agonists exert anti-hyperalgesic and/or antiinflammatory actions in vivo, possibly by interfering with the initiation of inflammation.