Aim To study the possibility that yellow wine polyphenolic compounds improves the pathological changes of atherosclerosis in vivo. Methods Six weeks old LDL receptor knock out mice （n40） treated with high-fat diet were randomly allocated to five groups （8 rats in each group）: high fat group, rosuvastain intervention group,yellow wine polyphenolic compounds 10 mg/（kg·d） intervention group, yellow wine polyphenolic compounds 30 mg/（kg·d） intervention group, yellow wine polyphenolic compounds 50 mg/（kg·d） intervention group, they received by sterile water, 10 mg/（kg·d） rosuvastain and yellow wine polyphenolic compounds with dose of 10, 30, 50 mg/（kg·d） dissolved in sterile water, respectively. High fat diet were given to establish the mouse model with atherosclerosis. After 16 weeks, they were sacrificed. The levels of plasma lipids in serum were examined. The morphological changes of aorta artery were observed under microscope. The expression of matrix metalloproteinase-2 （MMP-2）, matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of matrix metalloproteinase-1 （TIMP-1）, tissue inhibitor of matrix metalloproteinase-2 （TIMP-2） were determined by Western blot. The activation of MMP-2, MMP-9 were determined by Gelatin Zymography. Results Compared to high fat group, the levels of total cholesterol （TC）, low density lipoprotein cholesterol （LDLC） and triglyceride （TG） were significantly decreased in rosuvastain intervention group （P<0.01） except for TG, plasma TC and LDLC levels were significantly decreased in yellow wine polyphenolic intervention compounds groups （P<0.01）. The levels of plasma TC, LDLC and TG showed significant difference between yellow wine polyphenolic compounds intervention groups and rosuvastain intervention group （P<0.05）. No significant difference of plasma high density lipoprotein cholesterol （HDLC） level among groups were observed （P>0.05）. Compared to high fat group, the atherosclerosis lesion area in rosuvastain intervention group and yellow wine polyphenolic compounds 10, 30, 50 mg/（kg·d） intervention groups decreased by 74.14%, 18.51%, 40.09%, 38.42% （P<0.01）, respectively. Use of yellow wine polyphenolic compounds and rosuvastain significantly reduced the atherosclerosis lesion area （P<0.01）. The yellow wine polyphenolic compounds and rosuvastain could down-regulate MMP-2, MMP-9 expression and activities （P<0.01）, whereas expression of TIMP-1, TIMP-2 were up-regulated （P<0.01）. Conclusions The yellow wine polyphenolic compounds is similar to the role of rosuvastain, which can improve dyslipidemia, reduce the expression and activities of MMP-2, MMP-9, at the same time promote the expression of TIMP-1, TIMP-2, improve the pathologic changes of atherosclerosis, indicating that they have benefic effects on cardiovascular system.