〔Abstract〕 Objective To explore effect and mechanism of paeoniflorin-6′-O-benzenesulfonate(CP-25) on human aortic smooth muscle cell(HASMC) with insulin resistance(IR). Methods IR-HASMC was induced by 1 μmol/L insulin. We detected glucose consumption by glucose consumption assay kit. Cell proliferation, migration and apoptosis were detected by CCK-8, transwell and flow cytometry method respectively. The protein expression of GRK2, INSR, p-IRS, PI3 K and GLUT4 were determined by Western blot. The co-expressions of GRK2 and INSR, GRK2 and p-IRS were determined by co-immunoprecipitation. Results CP-25 increased the glucose consumption in IR-HASMC. CP-25 also inhibited abnormal proliferation and migration of cells, and promoted cell apoptosis. CP-25 down-regulated membrane expression of GRK2, up-regulated the expression of INSR, p-IRS, PI3 K and membrane expression of GLUT4. The co-expressions of GRK2 and INSR, GRK2 and p-IRS could be reduced by CP-25. Conclusion CP-25 can improve IR in HASMC, in which it inhibits the membrane translocation and expression of GRK2 and promotes activation of INSR/IRS/PI3 K/GLUT4 signaling pathway.