Acute and chronic osteomyelitis generally require long-term antibiotic therapy and surgical debridement. Implant-associated osteomyelitis, particularly from methicillin-resistant Staphylococcus aureus (MRSA) strains, is difficult to treat. Rifaximin is an antibiotic derived from rifamycin which may be effective in the treatment of osteomyelitis in terms of its wide spectrum of action and pharmacological properties. The aim of this experimental study was to investigate the local efficacy of rifaximin in rat models with MRSA and implant associated osteomyelitis. This study was carried out with 40 adult Wistar albino rats. The rats were randomly divided into 4 equal groups with 10 rats in each. An implant related MRSA osteomyelitis was created in the right tibia metaphysis of each rat by Norden's experimental osteomyelitis model. After 4 weeks, the implants of each tibia were removed and debridement was applied. Group 1 was designed as control group and no other treatment was applied other than debridement. Bone cement without any antibiotic was applied to Group 2, bone cement with teicoplanin was applied to Group 3 and bone cement with rifaximin was applied to Group 4. After 4 weeks from the second surgery, euthanasia was performed to the rats and the clinical, histopathological and microbiological results were compared. There was no statistically significant difference between the groups in clinical scoring. A statistically significant difference was found between the histopathological scores of Group 1 and Group 2 and the histopathological scores of Groups 3 and 4; the histopathological scores of Group 1 and Group 2 were found to be higher than Group 3 and Group 4. When the pre-and post-treatment colony numbers were compared, although there was a statistically significant difference between Group 3 and Group 2, no statistically significant difference was found between Group 4 and Group 1 results. In spite of its wide spectrum, the local efficacy of rifaximin in the treatment of osteomyelitis could not be demonstrated. This study shows the ability to shed light on some future comprehensive studies with the inclusion of infection markers.