A novel negatively thermo-sensitive and biodegradable microgel was prepared by combination of macromer synthesis and inverse suspension polymerization. A new post-fabrication encapsulation technique based upon this kind of intelligent microgel was developed. Model proteins (hemoglobin, bovine serum albumin and insulin) were encapsulated into the microgels at 4 degrees C and released in vitro at 37 degrees C. Relatively high loading levels and sustained release profiles demonstrate the feasibility of the encapsulation strategy. Since the encapsulation of proteins was performed at low temperature and after the preparation of microgels, organic solvent and high temperature were completely avoided in drug encapsulation. FTIR, Raman and circular dichroism measurements confirmed that the ordered structure of proteins was not destroyed during encapsulation and after release. Thus, the post-fabrication encapsulation technique in this paper is much unique and beneficial for controlled release of biomacromolecular drugs.