〔Abstract〕 Objective To establish an inducible macrophage-specific knockout G protein-coupled receptor kinase 2(GRK2) gene(GRK2flox/floxLyz2-CreERT+) mice model. Methods GRK2flox/floxLyz2-CreERT+mice were constructed based on Cre/LoxP system. The genotypes of GRK2flox/floxLyz2-CreERT+mice were identified by PCR amplification and agarose gel electrophoresis. After the mice were sacrificed by carbon dioxide method, the expression of GRK2 in bone marrow-derived macrophages(BMDMs) and peritoneal macrophages(PMs) was detected by Western blot. Immunofluorescence was used to detect GRK2 expression in mouse brain, heart and spleen macrophages. The M1/M2 ratio in PMs induced by prostaglandin E2(PGE2) was analyzed by flow cytometry. Results The results of genotype identification showed that the mice with a band at 355 bp in the length of the flox amplification product and a band at 355 bp in the length of the Cre amplification product were GRK2flox/floxLyz2-CreERT+mice. Western blot results showed that GRK2 expression in BMDMs and PMs of GRK2flox/floxLyz2-CreERT+mice decreased compared with GRK2flox/floxmice(P<0.01). Immunofluorescence results showed that GRK2 expression decreased in the brain, heart and spleen of GRK2flox/floxLyz2-CreERT+mice compared with GRK2flox/floxmice(P<0.01). Flow cytometry showed that compared with GRK2flox/floxmice, there was no significant difference in the proportion of CD86/CD206 in the PMs of GRK2flox/floxLyz2-CreERT+mice. Under PGE2(10 μmol/L) stimulation, the proportion of CD86/CD206 in GRK2flox/floxLyz2-CreERT+mice PMs increased(P<0.01). The proportion of CD86/CD206 in the PMs of GRK2flox/floxmice was higher than that of GRK2flox/floxLyz2-CreERT+mice(P<0.01). Conclusion In this study, GRK2flox/floxLyz2-CreERT+mice model was successfully constructed, and the mice promoted PGE2-induced polarization of PMs to M2-type macrophages compared with control mice.