〔Abstract〕 Objective To investigate the role of bufalin(BU) in inhibiting M2-type macrophage-mediated colorectal cancer metastasis. Methods Human acute leukemia mononuclear cells(THP-1) were differentiated into M0 macrophages using phorbol ester induction(PMA) for 48 hours. The M0 macrophages were then treated with IL-4 and IL-13 medium. Surface markers and morphological changes were observed through ELISA, morphology, and RT-qPCR experiments. RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages. The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA. Additionally, the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell, Wound healing, RT-qPCR, and Western blot experiments. Subsequently, bufalin was added to the conditioned medium and the changes in AKT/PI3K protein, migration, and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot, Transwell, Wound healing and RT-qPCR experiments. Results THP-1 were successfully differentiated into M2 macrophages. The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages, which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells. The migration and epithelial-mesenchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin. Conclusion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells, thereby promoting their migration and epithelial-mesenchymal transition capacity. Moreover, bufalin exhibits inhibitory effects on this effect.