This study relates to the Bovine Serum Albumin (BSA) protein-controlled release system with Poly(lactic-glycolic acid) (PLGA) biodegradable polymer. It also has special double emulsification carriers containing alkaline material of hydroxyapatite (HAp), which can carry the hydrophilic drug effectively and sustain a controlled substance release. The controlled release strategy is based on the HAp absorption ability, which will be trapped into the core of PLGA microsphere. Besides, the acidic degradation products of PLGA polymer and basic inorganic component of HAp can be used to control the dissolution of microsphere, then resulting in protein release. We have varied the HAp amount to observe its effect on microsphere characteristics such as the particle size, surface/internal morphology, BSA entrapment efficiency, microsphere degradation, BSA in vitro release behaviour, and cell toxicity etc.