Objective To investigate the protective effects of ulinastatin on acute lung injury ( ALI)induced by seawater drowning in rats. Methods Thirty male SD rats were randomly divided into three groups, ie. a control group, a model group, and an ulinastatin treatment group. The rats in the model group and the ulinastatin treatment group received intratracheal artificial seawater ( 4 mL/kg) instillation. Then the ulinastatin treatment group received ulinastatin ( 100 000 U/kg) injection after infusion of seawater while the model group received an injection of same amount of saline. The rats were sacrificed at 4 hours after instillation. The pathological changes of lung were evaluated by hematoxylin-eosin stain under light microscope. Lung wet/dry weight ratios were measured to assess the level of pulmonary edema.Concentrations of tumor necrosis factor ( TNF) -α, interleukin ( IL) -1β, IL-6, and IL-10 in bronchoalveolar lavage fluid ( BALF) were detected by enzyme-linked immunosorbent assay ( ELISA) . The myeloperoxidase activity in lung tissue homogenates were measured by colorimetric method. Results Ulinastatin treatmentsignificantly relieved the decline of PaO2 and lung pathological changes, inhibited myeloperoxidase activity,and reduced lung wet/dry weight ratios. Ulinastatin also inhibited the release of TNF-α, IL-1β, and IL-6,whereas increased the expression of IL-10 simultaneously. Conclusion Ulinastatin attenuates seawater induced ALI, which may be related to its inhibitory effects on inflammation reaction through regulating cytokine secretion.