Abstract: A method for preparing biodegradable microspheres having a three-dimensional network in which biologically active macromolecular agents are physically entrapped therein. The microsphere is able to degrade and release the macromolecular agent at a controlled rate. The method involves emulsifying a vinyl derivative of a biodegradable hydrophilic polymer, a water-soluble monovinyl monomer and a biologically active macromolecule in water, and copolymerizing the biodegradable hydrophilic polymer and the water-soluble monovinyl monomer such that the biologically active macromolecule is entrapped therein.