pH-sensitive bovine serum albumin (BSA) hydrophilic microspheres were prepared by free radical polymerization of methacrylate derivatized BSA and methacrylic acid sodium salt. Incorporation of both monomers in hydrogels was confirmed by Fourier transform infrared spectroscopy. Morphological analysis by scanning electron microscopy showed spherical shape and porous surface of all prepared samples. The microspheres showed high water affinity at neutral pH values and a narrow dimensional distribution. Network density of hydrogels depends on derivatization degree (DD%) of BSA and/or concentration of modified BSA in the polymerization feed. In order to employ the prepared samples such as pH-sensitive hydrogels, in vitro release studies, in media simulating biological fluids, were performed using diflunisal (DF) and beta-propranolol (PR) as model drugs. Experimental data showed that the release profiles depend on drug-matrix interactions and diffusional limitation awardable to crosslinking degree of microparticles. beta-Propranolol is quickly released at pH 1.0 and a complete release after 1 h at pH 6.8 was observed. In the case of diflunisal pH-sensitive release was observed. At pH 1.0 low amounts of drug were released (w/w<10% after 2 h). When the pH is 6.8, the diflunisal release increased in the amount (w/w>75% after 24 h).