Thermal and dual stimuli-responsive microspheres (pH and temperature) were prepared by free radical polymerization of methacrylate bovine serum albumin (BSA-MA) as cross-linker and sodium methacrylate (NaMA) and/or N-isopropylacrylamide (NIPAAm), as hydrophilic/pH-sensitive and thermo-responsive monomers, respectively. Microgels were characterized by infrared spectroscopy, morphological analysis, particle size distribution and determination of swelling properties. The network density and the shape of the microgels were found to depend on the concentration of the reactive species in the polymerization feed. Thermal analyses were performed to determine lower critical solution temperature values, which become close to the body temperature by increasing the content of the hydrophilic moieties in the network. In order to test the preformed materials as drug carriers, in vitro release studies of Diclofenac diethyl ammonium salt were performed. For all the co-polymers, a predominant drug release in the collapsed state was observed, while below the microgel transition temperature, a drug release through the swollen network occurs. The data recorded during the release tests demonstrated that the pH of the surrounding environment influences the drug release more than the temperature of the imbibing medium.