Abstract: Objective To develop an anti-infection nano-hydroxypatite (nano-HA) microsphere for local drug delivery for treating osteomyelitis. Methods The nano-HA was used as the core carrier to load gentamicin (GM) and coated with poly(-hydroxybutyrate-co-hydroxyvalerate)/polyethylene glycol (PHBV/PEG), which was degradable and biocompatible, to prepare nano-HA-PHBV/PEG-GM microsphere. The surface structure and in vitro drug-release of the microsphere were studied. Results The microsphere had good drug delivery capability. The samples weighing 90 mg each were soaked in PBS and gentamicin release within the first day was 165.2 μg/ml, which maintained a low release rate in the following days. After 28 days, gentamicin release declined to 8.5 μg/ml, which was higher than the minimal inhibitory concentration of gentamicin (2 μg/ml). Conclusion The local drug delivery system has good drug-release performance in vitro and may possess potential value in clinical management of osteomyelitis.