| Pasteurella multocida is the most critical respiratory bacterial infection of rabbits, around the globe. Beside passive immunization, anti-bacterial treatment is the primary choice of disease control. Since tulathromycin may be retained in the lung for many days after single administration, it can be applied for treatment of respiratory diseases. Hence, the purpose of current study was to evaluate the efficacy of tulathromycin in treating experimentally infected rabbits with P. multocida. In the sensitivity test, tulathromycin showed a potent inhibitory effect on P. multocida compared to several well-established antimicrobial agents. In vivo, treatment with tulathromycin improved clinical signs, mortality rate, lesion scores and growth performance parameters in infected rabbits. Furthermore, treatment with tulathromycin ameliorated the hematological picture, lowered the level of biochemical parameters which were significantly increased due to infection as liver enzymes, blood urea, creatinine and creatine kinase (CK-MB) and elevated the levels of total protein and albumin. Biochemical findings were supported by histopathological picture. It can be concluded that tulathromycin is an ideal and safe antibiotic for treating infection with Pasteurella multocida in rabbits.