Abstract: Objective To observe the effect of hydroxyethyl starch 130/0.4(voluven)on P38 mitogen-activated protein kinases(MAPK)signal transduction pathway,with the aim of investigating the mechanism of its protective effect on acute lung injury(ALI)due to infection.Methods Thirty male Sprague-Dawley(SD)rats were randomly divided into control group,lipopolysaccharide(LPS 10 mg/kg) group,voluven groups(LPS 10 mg/kg,and hydroxyethyl starch 130/0.4 15 ml/kg or 30 ml/kg)and alone voluven grouP(hydroxyethyl starch 130/0.4 30 ml/kg),with 6 rats in each group.Rats were sacrificed at 6 hours,the lungs were harvested for observation of pathological changes.The expression of p-P38,P38, p-P44/42 and P44/42 were detected with Western blotting.Activating protein-1(AP-1)activation was measured with electrophoretie mobility shift assay(EMSA).Results Compared with control,p-P38, p-P44/42 and AP-1 were significantly higher in LPS group(P<0.05 or P<0.01).The expressions of p-P38 and AP-l activation were significantly reduced in both voluven groups(all P<0.05).But there was no statistically signifleant difference between voluven 15 ml/kg and 30 ml/kg groups(all P>0.05).Conclusion Hvdroxyethyl starch 130/0.4 can inhibit LPS-induced ALI by depressing expression of p-P38 and AP-1 activation in lung.