Abstract: The aim of the present study was to clarify the pathway and mechanism involved in the anti-melanona effect of Scutellarin (SCU). CCK-8 and Transwell assays were employed to evaluate the cell proliferation and migratory abilities of B16 in vitro. Then, a B16 tumor-bearing mouse model was established to explore the effect of SCU on tumor growth in vivo. Immunohistochemistry and flow cytometry were also used to examine the effect of SCU on tumor angiogenesis and the mobilization of bone marrow-derived cells, respectively. The results showed that SCU substantially decreased the proliferation of B16 cells at doses of 160, 320, and 640 μmol/L, respectively (P<0.01). Moreover, the migration and invasion capacity of B16 cells were apparently reduced when treated with 160 and 320 μmol/L SCU. Besides, the growth of B16 cells in vivo was remarably slower after administration of 30 and 60 mg/kg SCU (P<0.01). Further immunohistochemistry semi-quantitative results revealed the microvascular density (MVD) of B16 tumor tissues was significantly decreased (P<0.01) and flow cytometry data shown that SCU could lower the cell counts of vascular endothelial growth factor receptor 2 positive (VEGFR₂⁺) bone marrow-derived cells (BMDCs) and Gr-1⁺CD11b⁺BMDCs in the peripheral circulating blood of tumor-bearing mice (P<0.01). In conclusion, SCU could inhibit the growth of B16 tumor cells in vitro and in vivo, which may be directly related to its inhibition of tumor cell function, as well as its inhibition of BMDCs mobilization, thus indirectly reducing tumor angiogenesis.