This paper deals with the synthesis of thermoresponsive microspheres with proteic structure exhibiting a transition temperature close to the body temperature. The hydrogels were synthesized by free radical polymerization of methacrylate Bovine Serum Albumin (BSA-MA) as crosslinker, and 2-hydroxyethyl methacrylate (HEMA) and/or N-isopropylacrylamide (NIPAAm), as hydrophilic and thermoresponsive monomers, respectively. The modification of the hydrophilic/hydrophobic balance in the polymerization feed allows to modulate the volume phase transition temperature of the macromolecular network. The hydrogels were characterized by infrared spectroscopy and thermal analyses, which showed negative thermoresponsive behavior for all compositions and, by increasing the content of the hydrophilic moieties in the network, the transition temperature was ranged from 34.2 to 36.8 degrees C. To test the preformed materials as drug carriers, diclofenac diethyl ammonium salt was chosen and drug entrapment percent was determined. Drug release profiles, in media at different temperature, depend on the crosslinking degree and on the composition of the hydrogels. By using semiempirical equations, the release mechanism was extensively studied and the diffusional contribute evaluated. The physic-chemical characteristics of thermoresponsive materials confirm the applicability of the microspheres as drug delivery device. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 342-351, 2011