〔Abstract〕 Objective To investigate the molecular mechanisms of advanced glycation end products(AGEs)-induced macrophage M1 polarization. Methods Primary M0 macrophages were isolated from mice bone marrow. Specific inhibitors of Toll-like receptor 4(TLR4) and receptors for AGEs(RAGE), namely TAK-242 and FPS-ZM1 were used to pre-treat the macrophages. Then the macrophages were exposed to AGEs at 2.5, 5 and 10 μmol/L respectively. Flow cytometry was used to detect intracellular reactive oxygen species(ROS) levels; immumofluorescence staining was used to observe the expression of M1 macrophage phenotype hall marker inducible nitric oxide synthase(iNOS); ELISA was used to determine the concentrations of inflammatory cytokines secreted from macrophages; Western blot was used to evaluate relative expression levels of cytosol and nuclear proteins. Results AGEs treatment induced elevation of intracellular ROS levels, interleukin 6(IL6), IL12 and tumor necrosis factor α(TNFα) concentrations, relative expression levels of cytosol TLR4, phosphorylated signal transducers and activators of transcription 1(p-STAT1) and nuclear STAT1 expressions in macrophages in a concentration dependent manner(allP<0.001). Pre-treatment of TAK242 significantly reduced iNOS expression, inflammatory cytokine concentrations, p-STAT1 expression and STAT1 nuclear translocation in AGEs-treated macrophages in a concentration dependent manner(allP<0.001) without affecting TLR4 expression and intracellular ROS levels. Pre-treatment of FPS-ZM1 significantly reduced iNOS expression, intracellular ROS levels(P<0.001), inflammatory cytokine concentrations(allP<0.001), TLR4 and p-STAT1 expressions(allP<0.001) and STAT1 nuclear translocation(P<0.001) in AGEs-treated macrophages. Conclusion AGEs can induce macrophage M1 polarization via RAGE/ROS/TLR4/STAT1 signaling pathway.