MCP2, aliased CCL8, has been suggested to be implicated in the metastasis of cancer cells; however, no direct evidence has been established in esophageal squamous cell carcinoma (ESCC). In our present study, to investigate the role MCP2 played in the metastasis of ESCC cells; in vitro cell co‐culture system was established. Wound‐healing and Transwell assays were used to evaluate the migratory and invasive variation of ESCC cells before and after treatment with recombinant human MCP2. It was shown that MCP2 was able to activate the NF‐κB signaling pathway inducing the epithelial‐mesenchymal transition (EMT) and promoting the migration and invasion of ESCC cells in vitro. Our study provides an alternative working mechanism for M2 macrophage mediated the metastasis in tumor microenvironment in ESCC.