Composite microspheres based on Ca-doped mesoporous silica and poly(L-lactic acid) (CaMCM-41/PLLA) were prepared by a solid-in-oil-in-water emulsion/solvent evaporation technique. Using gentamicin as a model drug, gentamicin was loaded in the microspheres by the adsorption method, and the in vitro release of gentamicin from the microspheres was evaluated in phosphorus buffer saline (PBS) solution at 37 °C. The results showed that the release rates of gentamicin from CaMCM-41/PLLA composite microspheres were much lower than that from pure PLLA microspheres. On the other hand, CaMCM-41 incorporation into PLLA had the ability to induce hydroxyapatite formation and deposited on the surface of CaMCM-41/PLLA composite microspheres during gentamicin releasing in PBS. Therefore, CaMCM-41/PLLA composite microspheres could potentially be used as a local drug release system for bone filling.