Common methods for bone regeneration have been used in autologous bone grafts. However, these methods have many disadvantages such as limited supply, harvest site morbidity, additional blood loss, and inflammatory response. A new approach using bone tissue engineering is based on the use of biodegradable scaffold in combination with osteoconductive or osteoinductive material to promote bone regeneration. Among synthetic polymers, PLGA is one of the most widely investigated materials with FDA approval. These composite microspheres possess excellent mechanical and biological properties. In this study, release kinetics of dexamethasone from these composite were investigated and cellular responses of osteoblast-like cells MC3T3-E1 to the composite microspheres were examined. HAp/Dex/PLGA composite microspheres were developed as bone substrate for bone regeneration. The HAp/PLGA composite microspheres were effective environment for the sustained release of Dex in comparison with PLGA microsphere loaded Dex for 14 days. The HAp/Dex/PLGA composite microspheres efficiently supplied not only the proliferation but also the differentiation of osteoblast, as demonstrated by alizarin red S, ALP activity, and calcium assay. The osteoconductive factor / osteoinductive factor / PLGA composite microspheres fabricated in this study can be used as potential materials of bone tissue engineering for bone regeneration.