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Objectives Statins have been shown to reduce cardiovascular morbidity and mortality by antiatherosclerotic effects on top of the cholesterol-lowering effect as well as potential pleiotropic effects. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. It has been demonstrated that statins could inhibit secretion of metalloproteinases from vascular smooth muscle cells and macrophages in vitro. This study investigated the effects of rosuvastatin on sterol synthesis and the expression of matrix metalloproteinases in LDLR-deficient mice. Methods LDLR-deficient mice on a high-fat and high-cholesterol diet developed plasma hyperlipemia and atherosclerosis. They were randomly given into rosuvastatin group (n=8), control group (n=8), and they were sacrificed after 12 weeks. We examined the levels of plasma lipid; the expression of MMP-2 and MMP-9 with zymography; the morphological of the aorta artery; the H&E and immunohistochemical with aorta sinus. Conclusions Rosuvastatin inhibits MMP-2 and MMP-9 expression and improves the progression of atherosclerosis in LDLR-deficient mice exposed to a high-fat and high-cholesterol diet. This may be one of the pleiotropic effects of rosuvastatin and benefits the therapy of many kinds of dyslipidemia, including familial hypercholesterolemia.