OBJECTIVE This study aims to investigate whether cefazolin-sodium has any adverse effect on fracture healing in an experimental rabbit model. METHODS The study was performed on 50 male New-Zealand white rabbits. Under general anesthesia, closed double fracture of middle one-third of the tibia-fibula of the left lower extremity of the subjects was produced by manual compression followed by closed reduction of fracture and long leg circular cast was applied. Subjects were divided randomly into five groups including 10 rabbits in each group. The first and second group were administered ciprofloxacin 50 mg/kg SC bid and cefazolin-sodium 50 mg/kg IM on the seventh day of fracture. The third group was applied a single high-dose of vitamin D (50.000 IU/kg) IM following fracture. The fourth group was applied daily vitamin E (alpha tocopherol) 20 mg/kg IM for five days from one hour before the production of fracture. Control group did not receive any treatment before and after fracture. Initial and control X-ray examinations were performed immediately and four weeks after production of fracture, respectively. At the end of the fourth week, animals were sacrificed and a histological examination of the fracture site was performed. RESULTS Histological evaluation showed that the histological grade of the fracture healing was significantly lower in the ciprofloxacin group, while it was significantly higher in the cefazolin-sodium, vitamin D and vitamin E groups, compared to control group (p<0.005). CONCLUSIONS Significantly improved histological grade of the fracture healing in subjects treated with cefazolin-sodium than controls suggest that it may be reasonable to choose cefazolin-sodium as an antibiotic therapy for the treatment of infection in patients with bone fractures.