Abstract: AIM:To investigate the influence of matrix metalloproteinase-9 on angiogenesis in atherosclerotic plaque stability and the effects of doxycycline. METHODS: Thirty six Wister rats were divided into groups A, B, and C. Rats in group B and C were fed a high-fat diet and received an i.p. injection of vitamin D3, whereas rats in group C were administered an i.p. injection of doxycycline. Serum lipids were measured by enzymatic and automatic biochemical analyzer, and serum MMP-9 levels were measured by double-antibody sandwich ABC-ELISA assay. Plaque morphology was observed by hematoxylin and eosin stain in aortic sections and the number of vulnerable plaques was counted. Neovessel density in the plaque was detected by immunohistochemical staining on the endothelial cell marker CD34. RESULTS: Serum cholesterol levels were similar between group B and C, but higher than levels in group A (P<0.05). Serum MMP-9 levels were markedly different among groups (P<0.05). Compared with group B, the number of vulnerable plaques was markedly reduced in group C. CONCLUSION: Doxycycline can enhance plaque stability. This effect may be accomplished by reducing the levels of MMP-9 and then inhibiting angiogenesis in atherosclerotic plaques.