Abstract: Objective：To investigate the protective effects of dexamethasone on ventilator-induced lung injury（VILI）in an rat model. Methods：We established an rat model of VILI with a large tidal volume of 40m/l kg.After anesthesia was administered and tracheotomy was performed，30healthy male Sprague-Dawley rats were randomly divided into three groups to receive two ventilation protocols for 4h： group A was served as control groups （n=10，V_T =8m/l kg），group B received large tidal volume ventilation （n=10，V_T =40m/l kg），group C（n=10） received the same tidal volume as group B with pre-treatment of dexamethasone.Arterial blood gases were measured every one hour.Total white blood cells （WBCs） in BALF were counted.Wet to dry right lung weight ratio （W/D），the concentrations of total protein in bronchoalveolar lavage fluid （BALF），TNF-α，IL-1βlevels in BALF and blood.Lung histopathology was assessed among three groups.Results：After 4hrs mechanical ventilation，arterial oxygen pressure（PaO₂） was significantly lower in group B than A and C.A large guantity of WBCs were found in BALF of group B.The total protein contents in BALF，W/D of right lung were significantly higher in group B than A and C.The levels of TNF-α，IL-1β in BALF were increased in group B，while decreased in group C.Histopathologic findings demonstrated more infiltrating WBCs ，destructive change of the alveolar wall in group B than other groups.Conclusions： These results suggest that a series of proinflammatory，inflammatory reactions may be involved in the course of VILI.Dexamethasone has obvious protective effects on VILI through its ant-i inflammation potents.