Objective: To observe the effects of dexamethasone and TLR4 in acute lung injury rats induced by freshwater drowning. Methods: Seventy-two rats were randomly divided into three groups:the control group,the freshwater drowning group and the dexamethasone group. A rat model of acute lung injury was induced by freshwater drowning by means of introduction freshwater into trachea of rats. At the time point of 0,0.5,2.0,4.0,8.0 and 24.0 h,the change of PaO2 was determined. At the time point of 0.5,2.0,8.0,and 24.0 h,the change of MPO,W/D and TLR4 mRNA in lung tissues,and the change of TNF-α and IL-6 in serum was determined. Results: Acute lung injury model induced by freshwater drowning was successfully reproduced in rats. Compared with the control group,PaO2 in the drowning group was decreased significantly at the time point of 0.5 h after infusion of freshwater,then elevated but maintained at a low level. The level of TNF-α and IL-6 in serum was increased at 0.5 and 2.0 h respectively. The value of W/D,MPO and TLR4 mRNA in lung tissues was enhanced at 0.5,2.0 and 8.0 h respectively. Dexamethasone alleviated lung injury induced by freshwater drowning through suppression of the expression of TLR4 mRNA and inflammatory factor. Conclusion: TLR4 may participate in acute lung injury induced by freshwater drowning,whereas,dexamethasone could suppress TLR4 mRNA and protect the lung from pulmonary freshwater drowning injury.