Abstract: Objective:To research the mechanism of isorhamnetin in treating insulin resistance,insulin-resistant Hepg2 cells were treated with isorhamnetin.Method:The MTT method was used to screen the safe dose of isorhamnetin. Hepg2 cells insulin resistance(IR)model was induced by high-concentration insulin treatment.The glucose oxidase method was used to measure the glucose content of the medium,to measure the effect of isorhamnetin on glucose metabolism in insulin resistant Hepg2 cells.The expression levels of AKT,p-akt,FOXO1,p-foxo1,G6pase,PEPCK and six proteins were detected by Western blot. Results:The safe dose of isorhamtin to Hepg2 cells was 1-3.8 μg/mL.Isorhamnetin effectively increased insulin resistance Hepg2 glucose consumption(P<0.05).Phosphorylation of AKT and FOXO1 proteins expression in insulin resistant(P<0.05)Hepg2 cells was promoted and the protein expression of G6pase and PEPCK was inhibited(P<0.05). The effect of isorhamnetin was comparable to metformin.Conclusion:Isorhamnetin can effectively improve insulin resistance of Hepg2 cells and achieve this effect by regulating the AKT-FOXO1 signaling pathway.