Polymeric sintered microsphere scaffolds have shown their tremendous potential in bone tissue engineering applications due to their highly porous and interconnected three dimensional structure and excellent mechanical properties. While these scaffolds are able to support basic cellular activity after seeding cells on them, the bioactivity of these scaffolds in terms of enhancing the biological performance of stem cells during bone regeneration is still under satisfactory. We hypothesized that incorporation of bioactive addictive such as hydroxyapatite into these scaffolds could improve their bioactivity without sacrificing the bulk properties of the scaffolds. We have successfully incorporated nano-hydroxyapatite (n-HA) into poly (lactic acid-glycolic acid) (PLAGA) microsphere based scaffolds in our previous studies. Herein, we aimed to evaluate the bioactivity of PLAGA/n-HA composite scaffolds, with a focus on studying the mineralization of the scaffolds in vitro. The capability of inducing apatite formation in vitro was largely enhanced in the composite scaffolds compared to plain PLAGA scaffolds. More importantly, PLAGA/n-HA composite scaffolds have been shown to improve rabbit mesenchymal stem cells (RMSCs) proliferation, differentiation, and mineralization as compared to control PLAGA scaffolds. Taken together, introduction of n-HA appears to be an efficient approach to improve the bioactivity of PLAGA scaffolds for bone tissue engineering.