Objective: The role of M2 macrophages infusion in dealing with obesity is still little known. In this study, the therapeutic effects of M2 macrophages infusion were investigated. Methods: High fat diet (HFD) was used to induce obesity in C57BL/6N mice. 5 x 10(5) M2 macrophages, derived from the bone marrow, were injected into obese mice through the tail vein twice with an interval of one week. Results: One week after the second injection, weight of inguinal adipose pad was significantly decreased. Accordingly, the adipocyte size of epididymal and inguinal adipose tissue (EAT and INAT) shrank. To our interest, we found that the infused M2 macrophages were homed to EAT, reversing the disturbed homeostasis of high Ml to low M2 in obese mice. Meanwhile, EAT with remodeled macrophages' homeostasis expressed less MCP-1, accompanying with decreased recruitment of inflammatory CCR2(+)CX3CR1(low)Ly6C(+) monocytes from the blood in M2 infusion group. Further, increased M2 in EAT contribute to enhanced expression of UCP1 expression in EAT, which helped to ameliorate insulin resistance and, subsequently, improve the serum level of triglycerides (TG) and low density lipoprotein cholesterol (LDL-c). Conclusions: These findings highlighted that M2 macrophages infusion could ameliorate obesity as well as obesity-related insulin resistance, suggesting an effective and healthy weight loss strategy. (C) 2017 Elsevier B.V. All rights reserved.