The aim of the present study was to investigate the effect of melatonin on the production of the inflammatory mediator prostaglandins in a model of acute inflammation, carrageenan-induced pleurisy, where prostaglandins are known to play a crucial role. The results show that melatonin (12.5, 25, and 50 mg/kg, intraperitoneally, 15 min before the carrageenan) inhibits the inflammatory response (pleural exudate formation, polymorphonuclear cell infiltration, and prostaglandin production) in a dose-dependent manner. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to cyclooxygenase-2 (COX-2) in the lungs of carrageenan- treated rats. Pretreatment of carrageenan-treated rats with melatonin (50 mg/kg, intraperitoneally, 15 min before the carrageenan) prevented COX-2 expression. The present results demonstrate that melatonin exerts potent anti-inflammatory effects. Part of these anti-inflammatory effects may be related to a reduction of prostaglandin production during the inflammatory process.