Objective To investigate the role of p38 mitogan-activated protein kinase signal transduction pathway in lipopolysaccha-ricle-indaced acute lung injury (ALI) in rats. Methods 48 wistar rats were randomly divided into 3 groups, saline control group (group A), lipopolysaccharide (LPS) group(group B) and SB203580 group(group C). Models of lipepelysaccharide-imluced ALI were used to oh-serve the expression of p38MAPK in rat lung, protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid (BALF) , pulmonary MDA content and the activities of serum NO. After LPS dripping for 6 hours, arterial blood was drawn for analysis and lung tissue was detec-ted. Results Compared with those in group A, expression of p38MAPK were markedly increased in group B and C (P<0.01). But in group C, expression of P38MAPK was significantly lower than that in group B (P<0.05). The protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid (BALF), content of pulmonary MDA and the activities of serum NO in group B, C were significantly higher than those in group A (P<0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in group B and C (P<0.01). Compared with those in group B, these indexes of lung injury were significantly lower while the level of arterial bicar-bonate and partial pressure of oxygen was increased in group C(P <0. 05 orP <0. 01). Under light microscope, the pathologic changes in-duced by LPS were significantly attenuated by SB2035g0. Conclusion The activation of P38MAPK play an important role in the mechanism of lipopolysaccharide-induced ALI.