Acid aspiration causes direct lung damage and secondary inflammatory response involving several cytokines and accumulation of neutrophils. Activated protein C (APC) exhibits antithrombotic and anti-inflammatory properties. We examined the effect and mechanism of pre-treatment APC on acid-aspirated lung injury in rats. Anesthetized rats were instilled intratracheally with normal saline (NS, 2 ml kg(-1)) or hydrochloric acid (HCl, 0.1 N, 2 ml kg(-1)). Thirty minutes before HCl instillation, APC (200 U kg(-1) h(-1)) was infused continuously into the right jugular vein. Animals were ventilated during the experiments. Five hours after HCl or NS instillation, bronchoalveolar lavage fluid (BALF) and lung tissue samples were obtained. Total and differential cell count, absorbance, albumin concentration, concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC) in BALF, wet and dry weight (W/D) ratio were measured. Platelet count and fibrin degradation product (FDP) in peripheral blood were also measured. HCl instillation markedly increased these values in BALF as well as W/D ratio. APC attenuated the parameters increased by HCl-induced lung injury in rats. However, HCl instillation and APC treatment did not cause significant changes in platelet count and FDP compared with the control. We conclude that APC treatment protected the rats against HCl-induced lung injury and that this action seemed to be due to the anti-inflammatory properties of this protein rather than its anti-coagulant effects.