Objective：This study aims to identify the role of AIM2（absent in melanoma 2）in the development of obesity in mice，explore the functioning cells and the regulation mechanism of obesity. Methods：AIM2 knockout mice and AIM2fl/fl Cx3cr1-Cre mice were given 60% high-fat food to induce obesity. The body weight changes of mice was monitored every week. HE staining was used to analyze the adipose tissue structure. Glucose tolerance and insulin sensitivity test was used to analyze the role of AIM2 in insulin resistance. Flow cytometry analysis was used to detect the changes of macrophage typing，and fluorescence quantitative PCR method was used to detect the expression of pro-inflammatory cytokines and anti-inflammatory cytokines. Results：In high-fat-induced obese mice，AIM2 was significantly down-regulated. The body weight of AIM2 knockout mice exhibit much higher than WT mice，and AIM2 knockout mice were less sensitive to insulin. What is more，the results of specific AIM2 knockout mice in macrophages AIM2fl/fl Cx3cr1-Cre were consistent with the full AIM2 knockout mice. In addition，bone marrow derived macrophages stimulated results in vitro confirmed that AIM2 promoted the polarization of macrophages into M1 type macrophages. Conclusion： AIM2 plays a protective role in the development of obesity in mice. It mainly regulates the occurrence of obesity by regulating the polarization of macrophages.