Macrophages, diversity and plasticity immune cells, participate in immune response and maintain homeostasis through M1/M2 phenotype transformation. Transient receptor potential melastatin 7 (TRPM7) is a widely expressed divalent cation channel with protein serine/threonine kinase activity, which has recently been found to affect macrophage proliferation and function. This study aimed to identify the role of TRPM7 in macrophage polarization. Our results suggested that TRPM7 was highly expressed in M1 type macrophages rather than M2-type macrophages. Interestingly, we detected that M1-type macrophages decreased while M2-type macrophages enhanced through blockade of TRPM7, which manifest as decreased TNF-a, iNOS and elevated Arg-1, CD206. Furthermore, blockade of TRPM7 could inhibit STAT1 phosphorylation and promote STAT6 phosphorylation. In conclusion, TRPM7 could regulate macrophage polarization via STAT1/STAT6 pathways. Taken together, it is suggested that TRPM7 might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. (C) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.