Objective Atherosclerosis has been linked to inappropriate vascular remodeling,which may result from the accumulation of inflammatory cells and the abnormal metabolism of extracellular matrix.It is presently unknown whether matrix metalloproteinases(MMPs) participate in the early pathological process.The aim of this study was to investigate whether MMPs are involved in atherogenesis in a cholesterol-fed rabbit model. Methods Forty-six New Zealand white rabbits were fed a diet containing 2% cholesterol and 3% lard.The rabbits were euthanized on day 0,and 8 after every 2 weeks to the end of 10th week.Aortic arch was excised and subjected to histological examination,immunohistochemistry and in situ zymography for MMPs and tissue inhibitor of matrix metalloproteinases(TIMPs).Atherosclerotic classification was according to AHA criteria.Results Based on HE staining,Sudan IV staining and macrophage immunostaining,the aortic arches were classified into five: normal artery(n8),initial lesion(n9),fatty streak (n8),preatheroma(n14) and atheroma(n7).During the progression of atherosclerosis,immunostained aortic slices showed that the triad membrane type 1-MMP(MT1-MMP),TIMP-2 and MMP-2,were colocalized with MMP-3 and TIMP-3,and increased in the hyperplastic intima concomitantly with elevated activities of gelatinolysis,caseinolysis,and migration of macrophages and smooth muscle cells.Conclusion During the early stages of atherogenesis,the modulation of MMPs is in a tendency towards activation,while collagen synthesis exceeds its degradation,which may contribute to the migration of macrophages and smooth muscle cells.