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Objective To investigate the mechanism of XiaoYaoSan in anti-tumor metastasis. Methods A mouse model of CT26.WT colon cancer xenograft and lung metastasis was established. In vivo imaging of small animals, lung tissue anatomy and HE staining were performed to evaluate the lung metastasis under different doses (200, 400 and 800 mg) of XiaoYaoSan intervention. Tumor M2 macrophage markers were detected by immunofluorescence and Western blot assay. Serum levels of transforming growth factor (TGF) -β and tumor necrosis factor (TNF) -α were detected by enzyme-linked immunosorbent assay (ELISA). The recruitment of VEGFR1+ myeloid cells in lung tissue was detected by flow cytometry. The expression levels of phosphatidylinositol 3-kinase (STAT3), vascular endothelial growth factor (VEGF) and premetastasis microenvironment markers matrix metalloproteinase (MMP) -9, S100A8 and Fibronectin were detected by Western blot assay. Results After XiaoYaoSan intervention, the lung metastasis was significantly reduced, expression levels of MMP-9, S100A8 and Fibronectin in lung tissue were significantly decreased, M1 polarization occurred in tumorassociated macrophages, the serum level of TGF- β was significantly decreased, and TNF- α level was significantly increased. The recruitment of VEGFR1+ myeloid cells was significantly decreased in lung tissue, STAT3 phosphorylation was inhibited, and VEGF expression was significantly decreased. Conclusion The antimetastatic activity of XiaoYaoSan is related to its ability to inhibit the pre-metastatic microenvironment, which may be realized by the phenotypic transformation of tumor-associated macrophages and inhibition of STAT3 signal transduction. [ABSTRACT FROM AUTHOR]