Abstract: Objective To observe the effect of decitabine (DAC) on macrophage polarization. Methods Bone marrow-derived macrophages (BMDMs) were obtained from six week-old C57/6L mice. The cell viability was detected by CCK8, western blot technique was adopted to detect macrophage phenotype changes treated by DAC. Macrophages were divided into control group, LPS group (LPS induced) and DAC group (LPS+DAC treatment), the levels of inflammatory factors were detected by qRT-PCR. The expression of macrophage subtype maker proteins was detected by western blot. Results Decitabine did not affect the activity and proliferation of macrophages. Compared with LPS group, DAC obviously depressed the expression of pro-inflammatory factors with IL-6 (99%) and CXCL10 (98%) decreasing most, and it upregulated anti-inflammatory factors with IL-4 increasing most by about 3 times (P＜ 0.05). Western blot results showed that DAC also obviously decreased M1 macrophage surface maker iNOS by 72% (1.4 vs 0.4, P=0.001) and upregulated M2 macrophage surface maker Arg-1 for 1.8 times with significant differences (0.5 vs 0.9, P=0.01). Conclusion Decitabine treatment can promote the polarization of macrophage to regulatory macrophage (M2) and restrain chronic inflammation.