Objective：To investigate the effect of mangiferin on glucose uptake in mouse myoblasts（C2C12） and its pharmacokinetic features in SD rats. Methods：After C2C12 differentiated into mature myotubes，it was divided into normal C2C12 cells（Nor-C2C12） and insulin resistance C2C12 cells（IR-C2C12） （palmitic acid modeling）. The glucose uptake of cells was observed after intervention with different concentrations of mangiferin. Then we administered 20 mg/kg mangiferin by gavage to 6 SD rats，and detected the blood concentration of mangiferin in the rats at different times by LC-MS，and analyzed its pharmacokinetic parameters. Results：The glucose uptake of IR-C2C12 was significantly lower than that of Nor-C2C12（P<0.01）. And whether it was normal cells or IR cells，mangiferin at higher doses（1 000，500，250 μg/mL） could significantly increase the glucose uptake of cells（P<0.01）. Pharmacokinetic study results showed：mangiferin HL_Lambda_z=1.34 h；Tmax=1.75 h；Cmax=90.65 ng/mL；AUClast=318.40 h·ng/mL；AUCINF_pred=327.10 h·ng/mL；MRTlast=2.47 h；Vz_F_pred=136.42 L/kg；Cl_F_pred=67.48 L/（h·kg）. Conclusion：Mangiferin has the activity of increasing the glucose uptake of C2C12 cells and alleviating the IR state of cells. This drug acts relatively quickly and has high bioavailability，which has the poten－tial to be developed into a good hypoglycemic drug or health care product.