Abstract: Objective: To investigate the effect of puerarin on insulin resistance (IR) in 3T3-L1 adipocytes and its possible mechanism.Methods: 3T3-L1 adipocytes were divided into 7 groups, namely control group, 3 μmol/L puerarin group, 10 μmol/L puerarin group, 30 μmol/L puerarin group, 100 μmol/L puerarin group, 300 μmol/L puerarin group, and positive control group (rosiglitazone 10 μmol/L group, RGZ group), with 6 Wells in each group.Cell proliferation was detected by MTT assay, and adipocyte differentiation was detected by oil red O staining.The IR model of 3T3-L1 adipocytes was established by dexamethasone induction, and the glucose utilization was measured after different concentrations of puerarin treatment.Cells were transfected to over-express TLR2 (Pue+oe-TLR2 group).The levels of TLR2 proteins were determined by western blotting and the levels of interferon-γ(IFN-γ)were determined by enzyme-linked immunosorbent assay(ELISA).Results: Compared with the control group, there was no significant change in the proliferation of 3T3-L1 adipocytes in the puerarin treatment groups (P> 0.05).Compared with the control group, the differentiation of 3T3-L1 adipocytes was significantly promoted in the puerarin treatment groups (P< 0.05).Compared with the control group, the glucose consumption of IR 3T3-L1 adipocytes was significantly increased in the puerarin treatment groups(P< 0.05).The expression of TLR2 and the secretion of IFN-γ in IR 3T3-L1 adipocytes were decreased, and the levels of GLUT4 and PPARγ were increased in the puerarin treatment groups (P< 0.05).The relative expression of TLR2 and the secretion of IFN-γ in the Pue+oe-TLR2 group were significantly higher than those in the Pue+oe-NC group, and the relative expression of PPARγ and GLUT4 was significantly lower than that in the Pue+oe-NC group (P< 0.01).Conclusion: Pue-rarin can increase the glucose consumption of IR3T3-L1 adipocytes and alleviate IR.Its mechanism may be related to the inhibition of TLR2 expression and the reduction of IFN-γ secretion.