Objective To explore the optimal combination parameters of calcium alginate microspheres by using high voltage electrostatic field technology,and to make microspheres with smaller and more uniform diameters for further study of the sustained release behavior of microspheres after drug loading.Methods Different voltage,CaCl2 concentration,and sodium alginate concentration were set.The centrifuge speed and needle diameter were observed.The diameter and surface morphology of the microspheres were observed.The optimal combination parameters were selected with smaller and more uniform diameters.Low,medium and high loads,three concentrations of bovine serum albumin,were named group L,group M and group H respectively.The encapsulation efficiency and drug loading rate of the three groups were compared.The cumulative slow-release curve was drawn and the sustained-release behavior in vitro was observed.Results Voltage of 16 KV,1 M CaCl2 concentration,0.5%sodium alginate concentration,200 r/min and 30 G needle were the best combination parameters.The encapsulation rates of group L,M and H were(91±1.46)%,(85±1.63)%,(79±3.29)%respectively.And the drug loading rates were(0.89±0.04)%,(2.56±0.57)%,(4.10±1.21)%respectively.All the three groups of drugs could be sustained for more than 28 days,the sustained release time was longer,and the release behavior was stable and regular.Conclusion The calcium alginate microspheres produced by using the optimal combination parameters are excellent drug delivery vehicles.