Abstract: Objective To observe the effect of Wenshen Yiqi medicine on the expression of matrix metalloproteinases(MMP-2,MMP-9) in rats with severe pneumonia. Methods Total 100 SPF SD rats were randomly divided into five groups:rats in control group were given normal feeding,and rats in the other four groups made severe pneumonia model by tracheal puncture injection model were given sterile distilled water and corresponding concentration of Wenshen Yiqi drink,1 times/d,treatment for 7 d.The Lung histopathological changes were observed,leukocyte and neutrophils of bronchoalveolar lavage fluid were accounted by Blood Analyzer,and the expression of lung tissue PI3K,AKT1,P-AKT1,MMP-2 and MMP-9 were detected by Western blot test. Results When compared with control group,the markers of other groups were significantly higher(P<0.05);compared with model group,the markers of middle and high dose group were significantly lower(P<0.05),but there was no significantly different with low dose group.There were no significantly different in PI3K and AKT1 protein expression between five groups(P>0.05).But there were significantly different in P-AKT1,MMP-2 and MMP-9 expression between five groups(P<0.05);As compared with control group,the markers of other groups were significantly higher(P<0.05);as compared with model group,the markers of low,middle and high dose group were significantly lower (P<0.05),and there were significantly different in each dose group(P<0.05).The relationship of MMP-2 and MMP-9 with P-AKT1 were positive correlation. Conclusion Wenshen Yiqi method can effectively reduce the expression of MMP-2 and MMP-9 through PI3K/AKT signaling pathway,reduce the degradation of extracellular matrix and inflammatory response,which might be one of the pharmacological mechanism for the treatment of severe pneumonia.