The aim of this research was to prepare microparticulate systems based on poly (lactide- co-glycolide) (PLGA) for the local release of ipriflavone in order to reduce bone loss. We developed the IP loaded PLGA microspheres using relatively simple oil-in-water (O/W) solvent evaporation method. HPLC was used to perform the in vitro release test of IP and morphology of cell attached on the microspheres was investigated using SEM. Cytotoxicity was assayed by cell counting kit-8 (CCK-8) test. Osteogenic differential cells were analyzed by ALP activity. Through RT-PCR analysis, we observed osteocalcin, ALP, and Type I collagen mRNA expression. The release of IP in vitro was more prolonged over 42 days and IP/PLGA microspheres showed the improvement on the cell proliferation, ALP activity and RT-PCR comparing with control (only PLGA). This initial research will be used to direct future work involved in developing this composite injectable bone tissue engineering system.