Tulathromycin is a new injectable macrolid antibiotic used for treating pulmonary disease. Therefore, the present work was aimed to study the effect of tulathromycin administration only or in a combination with vitamin C (immunomodatory agent) on immnomodulating, apoptotic effect and DNA of some immune cells. Moreover, to investigate its effect on serum antioxidant activity. Twenty-five apparently healthy rabbits were divided into 5 equal groups, the 1^st group was the control and the 2^nd was the vaccinated group with 1 mL/rabbit S.C “Pasteurella multocida vaccine". The 3^rd group injected with 17.5 mg/rabbit of vitamin C and 1 mL/rabbit S.C “Pasteurella multocida vaccine" while, the 4^th group was given 1 mL S.C/rabbit Pasteurella multocida vaccine and 2.5 mg/kg BW tulathromycin. The 5^th group was treated S.C with 17.5 mg/rabbit vitamin C, 1 mL Pasteurella multocida vaccine and 2.5 mg/kg BW tulathromycin. The results showed a significant inhibition of lymphocyte transformation at 3^rd day, phagocytic activity and lysozyme activity at 1^st, 2^nd and 3^rd day of vaccination in the 4^th group. Moreover, its total globulin level was significantly depressed at the 7^th and 14^th day with a depression of antibody titre against pasteurella till the 3^rd week post vaccination. Comet results revealed a significant increase of DNA damage % on the 3^rd and 7^th days post vaccination. DNA fragmentation of neutrophil was transiently occurred in the 3^rd and 7^th days post treatment. It was concluded that, Tulathromycin has a transient immunosuppressive and genotoxic effect, therefore it should be administered in a combination with Vit C to overcome its side effects.