To investigate the effect of partial liquid ventilation (PLV) at low inflation pressures on acute lung injury (ALI), endotoxin was administered to healthy anesthetized juvenile piglets. The animals were randomly assigned to two groups, n=6 each: (1) conventional mechanical ventilation (MV) and (2) PLV with perfluorodecalin (10 mL kg(-1)). Compared with MV, PLV improved each cardiopulmonary variable measured. These variables included pulse contour cardiac output, heart rate, blood pH, breathing rate, both partial pressure of arterial oxygen (PaO2) and PaO2/FIO2 (fraction of inspired oxygen), partial pressure of arterial carbon dioxide (PaCO2), dynamic lung compliance, tidal volume, and ventilation efficacy index. Lung morphology also showed less damage in the PLV group, even in non-dependent regions (P<0.05). Our data support the hypothesis that PLV can decrease pulmonary damage, improve gas exchange and cardiac output, and may lead to a better prognosis in endotoxin-induced ALI.