In vitro, when cells were incubated alone, DM caused M1 polarization of macrophage, evidenced by increased iNOS and decreased CD206 expressions, and obvious dysfunctions of HUVECs; DM‐induced injury of endothelial cells was significantly worsened when the two cells were co‐cultured; addition of sitagliptin markedly reversed changes of macrophage but not of HUVECs in DM when cells were cultured alone; when cells were co‐cultured, however, both abnormal macrophage polarization and endothelial impairment in DM was significantly alleviated by sitagliptin. The gene discussed is MRC1; the disease is diabetes mellitus.