Ischemia-reperfusion not only damages the affected organ but also leads to remote organ injuries. Hepatic inflow interruption usually occurs during hepatic surgery. To investigate the influence of liver ischemia-reperfusion on lung injury and to determine the contribution of tidal volume settings on liver ischemia-reperfusion-induced lung injury, we studied anesthetized and mechanically ventilated rats, in which the hepatic inflow was transiently interrupted twice for 15 minutes. Two tidal volumes, 6 ml/kg (IR-LT) and 24 ml/kg (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation (NC-LT and NC-HT, respectively). Both the IR-HT and IR-LT groups had a gradual decline in the systemic blood pressure and a significant increase in plasma TNF- concentrations. Of the 4 groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet to dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the BAL fluid TNF- concentration. Furthermore, only in the IR-HT group was airway pressure increased significantly during the 6 h reperfusion period. These findings suggest that liver ischemia-reperfusion caused systemic inflammation, and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.