Abstract: Objective: To investigate the effect of endostatin and doxycycline on melanoma cell proliferation and tu-mor angiogenesis. Methods: Murine B16 melanoma experiment was performed. The mice were divided into 4 groups: theendostatin group(E group), the doxycycline group(D group), and group treated with endostatin and doxycycline(DE group),and the control group with no treatment (C group). HE staining was performed to compare the tumor necrosis rate and mi-cro-vessel density (MVD) among these groups. Immunhistochemistry was employed to detect the expression of proliferatingcell nuclear antigen(PCNA). Results: The MVD in the three experimental groups were all less than in the control group(F=10.888, P<0.05), indicating that doxycycline and endostatin inhibited tumor angiogenesis. By decreasing blood supply fortumor, doxycycline and endostatin inhibit tumor cell proliferation and promote tumor cell necrosis. Tumor cell necrosis ratein the three experimental groups were all higher than in the control group(F=7.229, P<0.05). PCNA expression in the threeexperimental groups were all statistically less than in the control group (F=17.729, P<0.05). Conclusion: The combinationof endostatin and doxycycline can influence PCNA expression and angiogenesis in melanoma, and can remarkably inhibitthe melanoma cell proliferation.