Background Pediatric patients are susceptible to lung injury. Acute lung injury in children often results in high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-a in an immature piglet model of acute lung injury induced by oleic acid (OA). Methods Twelve Chinese immature piglets were induced acute lung injury by OA. The animals were randomly assigned to two groups of six animals, (1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group. Results Compared with MV group, the PLV group had better cardiopulmonary variables (P <0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/inspired O-2 fraction (FiO(2)) and partial pressure of arterial carbon dioxide (PaCO2). PLV reduced TNF-a levels both in plasma and tissue compared with MV group (P <0.05). Conclusion PLV provides protective effects against TNF-alpha response in OA-induced acute lung injury in immature piglets. Chin Med J 2012;125(1):123-128