In this study, a newapproach for protein delivery is introduced, involving biodegradable porous poly(d,llactic-co-glycolic acid) (PLGA) microspheres blockedwith calcium alginatehydrogel. Porous microsphereswere prepared by solvent evaporation method using sodium oleate as an extractable porogen. The resultantmicrospheres show porous surface and three-dimensional network structure with interconnectingpores. Human serum albumin (HSA) used as model protein, was adsorbed into micropores of porousmicrospheres by a solution immersing method. Thus, the harsh preparation conditions, such as the aqueous/organic interface produced by awater-in-oil microemulsion and the acute shearing strength broughtby a high-speed homogenizer or a sonicater, inducing protein denaturation and aggregation could beavoided. Then, calcium alginate hydrogel was fabricated to block micropores of protein-loaded porousmicrospheres. A sustained protein release in vitro could be achieved in this way. Furthermore, it is noteworthythat the protein maintained its structural integrity after this preparation. The porous polymericmicrospheres may have great potential application for water-soluble drugs, such as protein, vaccine andgene delivery.