In this study, the effect of clarithromycin on the destruction of bacterial biofilm in Pseudomonas aeruginosa osteomyelitis was investigated. Foreign body-related osteomyelitis caused by ceftazidime-sensitive Pseudomonas aeruginosa was produced in the tibias of 26 rats. After osteomyelitis was verified on Day 14, 10 rats had ceftazidime (1500 mg/kg/day) given subcutaneously, and 10 rats had ceftazidime given subcutaneously and clarithromycin (100 mg/kg/day, two 50-mg/kg doses every 12 hours) given orally; three rats formed the control group. After a treatment period of 20 days, the tibias and the foreign bodies were removed, cultured, and examined by electron microscopy. The number of microorganisms growing on the bone tissue in the group receiving combined treatment was significantly lower than in the other groups. The number of microorganisms growing on the foreign body in the group receiving only ceftazidime was significantly higher than that of the group receiving combined treatment. Electron microscope examination revealed that the biofilm layer was eradicated in the group that had combined therapy; however, biofilm formation was evident on the foreign body in the group receiving only ceftazidime. Clarithromycin enhanced the activity of concomitantly used bactericidal agents by destroying biofilm on the surface of the materials.