Objective To investigate the effect and mechanism of Astragalus and Hirudin on Glomerular Mesangial proliferation and the levels of MMP-9 and NF-κB. Methods Twenty-five female mice were randomly divided into 5 groups, named normal group, model group, and intervention groups which areastragalus polysaccharide group, astragaloside group and hirudin group respectively; 5 mice in each group.After lipopolysaccharide induced the proliferation of mesangial cells in mice, CCK8 method was used to detect the active ingredients of the maximum non-toxic concentration of astragalus and leech. Cells were collected and flow cytometry was used to detect the apoptosis of each group after 24h; Immunocytochemistry and qPCR were employed for detecting the expression of MMP-9 and NF-κB. Results The apoptosis rate of each intervention group was higher than that of the model group and the normal group (P<0.05); Compared with the model group, the expressions of MMP-9 and NF-κB in each intervention group were significantly reduced, but were higher than that of the normal group (P<0.05). Conclusion The different active ingredients in Astragalus and Leech may reduce the expression of MMP-9 and NF-κB protein, inhibit the release of inflammatory factors and degrade the extracellular matrix, thereby protecting the renal basement membrane to inhibit mesangial cell proliferation so as to avoid kidney damage.