By a double emulsion solvent evaporation method, interferon-alpha (IFN-alpha) microspheres were prepared with poly(lactide-co-glycolide) (PLGA) and their characteristics, such as morphology, drug loading, encapsulation efficiency, in vitro release and degradation were evaluated. The IFN-alpha microspheres were prepared by different viscosities from 0.17-1.13 dL g(-1) and concentrations between 5-25% of PLGA, which not only affected the drug loading and encapsulation efficiency of IFN-alpha microspheres, but also strongly influenced the in vitro release. With smooth and porous surface, the drug loading and encapsulation efficiency of the microspheres prepared by 15% 0.89 dL g(-1) PLGA were 7.736% and 77.38%, respectively. The DSC curve of microspheres indicated IFN-alpha was loaded inside the microspheres. The degradation of microspheres was homogeneous and the mass loss was over 80% in 6 weeks. The release profile of microspheres showed a sustained fashion and the IFN-alpha released from microspheres maintained its bioactivity for 7 days.