〔Abstract〕 Objective Tnfrsf11 a Cre Rosa26 yfp reporter gene mice were prepared to determine the efficiency of Cre-mediated recombination using flow cytometry in different tissue-resident macrophages. Methods TheTnfrsf11 a Cre Rosa26 yfp reporter mice were generated by crossingTnfrsf11 a Cre mice withRosa26 yfp mice and identified by PCR.Brain microglia, liver macrophages, kidney macrophages, alveolar macrophages and spleen macrophages were separated from adultTnfrsf11 a Cre Rosa26 yfp reporter mouse and yellow fluorescent protein(YFP) labeling efficiency was analyzed by flow cytometry. Results YFP expression percentage was about 91.27% of brain microglia inTnfrsf11 a Cre Rosa26 yfp reporter mice, but liver, spleen, and alveolar macrophages were inefficiently targeted(63.60%,69.66%,32.76%). Conclusion Tnfrsf11 a Cre mice were qualified as conditional knockout model mice of brain microglia andTnfrsf11 a Cre Rosa26 yfp reporter mice can be used as a tool for conditional knockout of brain microgliain vivo.