Aim To approach the possible mechanism of Guanxinshutong capsule on the progression and stability of atherosclerotic plaque through observing the effects of Guanxinshutong capsule on pathologic morphology and expression of tissue matrix metalloproteinase inhibitor-1 （TIMP-1）, matrix metalloproteinases-9 （MMP-9） of atherosclerotic plaque in ApoE^－/－ mice model with experimental atherosclerosis. Methods The animals were fed with high fat diet. They were randomly divided into 3 groups when they were 20 weeks old （10 mice in every group）. They were high fat diet fed group （HF）, high fat diet and high-dose Guanxinshutong capsule ［1.8 g/（kg·d）］ group （HH）, high fat diet and low-dose Guanxinshutong capsule ［0.6 g/（kg·d）］ group （HL）. All the animals were fed for 12 weeks.After administered for 12 weeks, mice were sacrificed. The area and thickness of atherosclerotic plaque were observed by the methods of oil red O and HE stain. The expressions of TIMP-1, MMP-9 in the plaque were detected by immune fluorescence staining method. Results Compared with HF group, the changes of the area and thickness of atherosclerotic plaque in HH group and HL group were obvious （P<0.05）. The expression of TIMP-1 didn’t have significant differences between groups （P>0.05） and MMP-9 in treatment groups were lower than those of model group （P<0.05）. Moreover, Significant differences were also observed between treatment groups （P<0.05）. Conclusion Guanxinshutong capsule can inhibit the formation and progression of atherosclerotic plaque and stabilize the unstable plaque through down-regulating the MMP-9 expression in atherosclerotic plaque, inhibiting the collagen decomposition.