Berberine Hydrochloride microspheres were prepared by emulsification-chemical cross-linking method using gelatin as carrier.With the encapsulation efficiency and drug loading as evaluation indexes,the effects of gelatin concentration,dosage and oil-water ratio were investigated by Box-Behnken design and response surface method.Scanning electron microscopy (SEM),Fourier transform infrared spectroscopy (FT-IR),X-ray diffraction (XRD),differential scanning calorimetry and thermogravimetric analysis (DSC & TG) were used for characterization.At the same time，the drug release property was evaluated with the drug release in vitro.The optimal prescription was determined as follows:the optimum gelatin mass fraction was 12%,the dosage was 25% and the oil-water ratio was 4.79.The drug loading rate and encapsulation rate of microspheres prepared by the optimized prescription was (19.97±0.17)% and (67.71±0.93)%,respectively.The microspheres had a round appearance with an average particle size of (131.81±1.58) μm.The results of DSC,XRD and FT-IR spectroscopy showed that berberine hydrochloride was present in the microspheres in an amorphous form.The cumulative release rates in vitro of 12 h were about 91% and 95% in phosphate buffered solutions at pH 2.5 and 7.4,respectively indicating that the gelatin microspheres had a sustained release effect.