Objective：To investigate the effect of ten-eleven translocation 2 protein（TET2） on expression of interleukin-1 receptor-related kinase-M（IRAK-M） in macrophage，and to investigate the upstream signaling pathway for TET2 expression induced by bacte－rial endotoxin/lipopolysaccharide（LPS）. Methods：LPS was used to stimulate macrophage cell line RAW264.7 in mice to induce endotoxin tolerance；qPCR and Western blot were used to detect the expression of IRAK-M and TET2 at different time points of LPS stimulation and endotoxin tolerance. After interference of siRNA toTET2 expression，qPCR and Western blot were used to detect the effect on IRAK-M expression. Cells were pretreated with mitogen-activated protein kinase（MAPK） signaling pathway inhibitors，and stimulated with LPS；qPCR and Western blot were used to detect the effect on TET2 expression. Results：TET2 and IRAK-M pro－tein continued to express after endotoxin tolerance in RAW264.7 cells，and its expression pattern was opposite to cytokines expression pattern. Expression of IRAK-M mRNA（P=0.000） and protein level was inhibited by interfering TET2 expression. Inhibition of MAPK signaling pathway was able to inhibit TET2 expression. Conclusion：MAPK signaling pathway up-regulates TET2 expression during macrophage inflammatory response，and TET2 promotes endotoxin tolerance by promoting IRAK-M expression.