Hydroxyapatite(HA) nanoparticles with hydrophobic surface have been synthesized using mono-alkyl phosphate (MAP) as modifier by hydrothermal synthesis method. The drug-loaded nano-HA/ Poly(ε-caprolactone)（PCL）composite microspheres and drug-load PCL microspheres were fabricated by an S/O/W emulsion solvent evaporation method. The microspheres morphology was investigated by scanning electron microscopy (SEM). Drug distribution in microsphere matrix was studied by confocal laser scanning microscope (CLSM). The results showed that the drug distributed evenly in the drug-HA-PCL microspheres, but only around the surface of the drug-PCL microspheres. The drug release profile showed that the nano-HA/PCL hybrid microspheres had low initial burst and could release continually for 90 days. This kind of hybrid microspheres can be used as a promising long-term drug delivery system in the bone.