Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies.Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury.The aim of this study is to investigate the effect of total liquid ventilation on oleic acid (OA)-induced lung injury in piglets.Methods Twelve Chinese immature piglets were induced acute lung injury by OA.Twelve piglets were randomly treated with conventional gas ventilation (control group) or total liquid ventilation (study group) for 240 minutes.Samples for blood gas analysis were collected before,and at 60-minute intervals after OA-induced lung injury.The degree of lung injury was quantified by histologic examination.The inflammatory cells and the levels of IL-1β,IL-6,IL-10 and TNF-α in plasma,tissue and bronchoalveolar lavage were analyzed.Results Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group (P＜0.05).The total lung injury score was also reduced in the study group (P＜0.05).The cconcentrations of IL-1β,IL-6,IL-10and TNF-α in plasma,tissue and bronchoalveolar lavage were significantly reduced in the study group (P＜0.05).Conclusions Total liquid ventilation reduces biochemical and histologic OA-induced lung injury in piglets.