Penicillin, the recommended treatment for rabbit syphilis, sometimes induces adverse effects. The efficacy of oral chloramphenicol was evaluated in 39 cases of rabbit syphilis to establish a safe and efficient treatment for this disease in companion rabbits. All cases clinically improved and recovered promptly. Fourteen of 39 cases (35.9%) relapsed, but most remained chloramphenicol sensitive. Since safety take priority over efficacy in treating syphilis in companion rabbits, chloramphenicol should be chosen as a first-line agent, as a general rule. Three-week administration of chloramphenicol may be adequate at the initial onset of disease. When relapse occurs repeatedly or the rabbit owner cannot administer the medicine adequately, treatment with penicillin should be considered.