〔Abstract〕 Objective To explore the effect of wogonoside(WG)on theKrüppel-like factor4(KLF4)/nuclear factor κB(NF-κB) pathway of RAW264.7 macrophages subject to high glucose stimulation. Methods RAW264.7 macrophages were cultured and the concentration range of inactive effect of WG on cells was detected by CCK-8.Macrophages randomly grouped into LG group(medium for 5.5 mmol/L of glucose), D group(30 mmol/L mannitol medium), HG group(medium for 30 mmol/L glucose), LG+WG50 group(5.5 mmol/L glucose + 50 μmol/L WG), HG+WG12.5 group(30 mmol/L glucose+12.5 μmol/L WG), HG+WG25 group(30 mmol/L glucose+25 μmol/L WG), HG+WG50 group(30 mmol/L glucose+50 μmol/L WG). The expression of inducible nitric oxide synthase(iNOS) in cells of each group was determined by immunofluorescence. NF-κB p65, NF-κB pp65, KLF4, iNOS, interleukin-1β(IL-1β), tumor necrosis factor alpha(TNF-α) expression in each group was detected by Western blot. mRNA expression of KLF4, iNOS,IL-1β, TNF-α in each group was detected by qRT-PCR. IL-1β, TNF-α secretion of cells in each group was detected by ELISA. Results Compared with LG group, the expression of iNOS in HG group was higher(P<0.01), and the expression of iNOS in HG+W50 group was lower than that in HG group(P<0.01). Compared with the LG group, high glucose can inhibit KLF4 expression(P<0.01), stimulate NF-κB pp65, iNOS,IL-1β, TNF-α expression(P<0.01), and increase the IL-1β, TNF-α level in the supernatant(P<0.01); However, the inflammatory index in the WG groups significantly decreased(P<0.01), but expression of KLF4 dose-dependent increased(P<0.01). Conclusion WG inhibits the expression of inflammatory factors and associated proteins secreted by macrophages by high glucose, and has the therapeutic effect of improving the protective factor-KLF4.