Abstract: To investigate the function of peripheral blood circulating endotheliocytes and myelogenic mesenchymal stem cells (MSC) in the process of angiogenesis in melanoma. Methods: ECV304 endotheliocytes marked with BrdU were inoculated into the tail vein of SCID melanoma tumor-bearing mice and then anti- BrdU immunohistochemical staining was performed on sections of the tumor tissues. Myelogenic MSC in the bones of fetal mouse limbs retrieved through the induction of labor through artificial rupture of membranes were sorted by FACS and amplified in vitro. After PKH26 staining, the MSC were inoculated into the SCID LiBr melanoma tumor- bearing mice through the tail vein. New vessels in the tumor were observed using fluorescent microscopy. The MSC without PKH26 staining were inoculated into the SCID B16 melanoma tumor- bearing mice through the tail vein. The animals were sacrificed 14 days after inoculation and the angiogenesis in the tumor tissue was studied using fluorescent in situ hybridization (FISH) and immunofluorescence technologies. Results: The results of the BrdU immunohistochemical staining showed that the positive ECV304 cells functioned as vascular endothelial cells (VEC) in the process of angiogenesis in the tumor tissue. In the melanoma, the PKH26-stained MSC induced differentiation and proliferation and then functioned in the tumor neovascularity. FISH and immunofluorescence staining showed that the myelogenic MSC could take part in the tumor neovascularity. Conclusions: In the process of malignant tumor growth, not only the VEC around the tumor can participate in the tumor neovascularity by pullulation, but the myelogenic MSC can also take part in the process of tumor angiogenesis.