Objective To explore the role of ulinastatin (UTI) in the treatment course of ventilator-induced lung injury (VILI) by investigating the effect of UTI on expression of Clara cell secretory protein (CC16) in the lung of rats in high tidal volume mechanical ventilation. Methods Twenty-four male Wistar rats were randomly divided into three groups:control group，high tidal volume ventilation group and UTI pretreatment group. The levels of MDA in the lung and total protein in bronchoalveolar lavage fluid ( BALF) were measured. The expression of CC16 mRNA in the lung was detected by reverse transcription polymerase chain reaction (RT-PCR) . The number of Clara cells and synthesis of CC16 were detected by immunohistochemistry. Results Comparing with the control group，the levels of MDA in lung and total proteinin bronchoalveolar lavage fluid were very significantly increased ( P < 0. 01 ) in the high tidal volume ventilation group，and the expression of CC16 was significantly decreased ( P < 0. 01 ) . Comparing with the high tidal volume ventilation group，the levels of MDA in the lung and total protein in bronchoalveolar lavage fluid were significantly decreased (P < 0. 01 ) in the UTI-pretreatment group，and the expression of CC16 mRNA and protein increased significantly. Conclusions CC16 plays an important role in ventilator-induced lung injury (VILI) . The expression of CC16 mRNA and protein are reduced in a VILI rat model. Ulinastatin may effectively prevent the inflammatory process and ventilator-induced lung injury by increasing the level of CC16 and inhibit the lipid peroxidation.