Abstract: Objective To investigate the effects of ailanthone on the invasion and metastasis of melanoma cells. Methods CCK-8 assay was used to detect the effects of ailanthone on the growth of human melanoma A375 cells. Invasion assay was employed to test the effects of ailanthone on the invasion of A375 cells.The expression of MMP-2 and MMP-9 was determined by Western blot. A lung metastatic model was established using murine melanoma B16-F10 cells to determine the anti-metastatic effects and toxic effects of ailanthone in vivo. Immunohistochemistry assay was used to detect the expression of MMP-2 and MMP-9 in the metastatic nodules. Results The growth of A375 was inhibited after ailanthone treatment. Furthermore, ailanthone significantly inhibited the invasion of A375 cells and reduced the expression of MMP-2 and MMP-9.Ailanthone also relieve the lung metastasis of B16F10 murine melanoma cells in vivo. However, no significant weight loss nor histopathological abnormalities was observed in the major organs of mice after ailanthone treatment. Conclusions Ailanthone inhibits the invasion and metastasis of melanoma cells.