Osteomyelitis is an inflammatory bone disease caused by pyogenic bacteria. The advantages of localized biodegradable therapy for osteomyelitis include high local antibiotic concentration at the site of infection and obviation of the need for removal of the implant after treatment. The purpose of this study was to develop and evaluate a biodegradable implantable delivery system containing gatifloxacin (GAT) for the localized treatment of osteomyelitis, experimentally induced by methicillin resistant Staphylococcus aureus (MRSA). Implants, prepared by solvent casting technique, showed reasonable tensile strength. DSC examination indicated that GAT is present in an amorphous form in the implant. The in vitro release of GAT showed a profile characterized by an initial burst followed by a second stage of gradual delivery over 27 days. The in vivo release study revealed that GAT concentrations achieved during the first 3 weeks after implantation exceeded the MIC of GAT against MRSA by > 100,000 times. Bacterial tibial bone count performed in rabbits tibia 2 and 4 weeks after implantation of GAT implant in infected bone indicated complete eradication of infection in all treated rabbits as indicated by the significant decrease in bacterial count. The results show that the proposed implant may have a promising role in the therapeutic approach to osteomyelitis.