〔Abstract〕 Objective To investigate the role of interleukin-8 (IL-8) secreted by tumor-associated macrophages (TAMs) in colorectal cancer (CRC) metastasis and its potential therapeutic value. Methods The TAMs model was constructed by phorbol ester (PMA) combined with IL-4/IL-13, and the model phenotype was verified by flow cytometry, RT-qPCR and ELISA. Human CRC HCT116 cells were treated with conditioned medium (CM) from M0 macrophages and TAMs, and the metastatic capacity of HCT116 cells was evaluated by wound-healing assay and Transwell assay. The expression levels of IL-8 in M0 macrophages and TAMs were detected by Western blot, RT- qPCR and ELISA. The expression level of epithelial-mesenchymal transition (EMT) markers (E- cadherin, N-cadherin) in HCT116 cells treated with CM-M0 and CM-TAMs were detected by Western blot and RT-qPCR. HCT116 cells were stimulated with CM-TAMs supplemented with IL- 8 receptor inhibitor Reparixin. The HCT116 cells metastasis ability was evaluated by wound-healing assay and Transwell assay, and the expression levels of E-cadherin and N-cadherin were detected by Western blot and RT-qPCR. Finally, a splenic injection liver metastasis model was established using murine CRC cells CT26-LUC, and the effect of Reparixin on this animal model was observed by in vivo imaging. Results Flow cytometry showed that the proportion of M2 macrophages (CD11b+CD206+ cells) was elevated in the TAMs model. RT-qPCR and ELISA assays revealed that the levels of M2 macrophage markers IL-10 and TGF-βsignificantly increased. Wound-healing assay and Transwell assay demonstrated that CM-TAMs significantly enhanced the migration and invasion ability of HCT116 cells. Western blot, RT-qPCR and ELISA assays showed that TAMs highly expressed IL-8 and simultaneously induced downregulation of E-cadherin and upregulation of N-cadherin in HCT116 cells. Reparixin not only reversed the pro-metastatic effects of CM-TAMs, but also upregulated the expression level of E-cadherin and downregulated that of N-cadherin in HCT116 cells. Furthermore, it reduced the bioluminescence signal intensity of liver metastatic lesions in the splenic injection liver metastasis model. Conclusion The TAMs promote CRC metastasis by secreting IL-8 to induce EMT. Inhibiting IL-8 secretion in TAMs or blocking the binding of IL-8 to its receptor may provide a new strategy for CRC treatment.