Zinc (Zn) plays a pivotal role in highly proliferative tissues including immune system. The long-term therapy of neoplastic and autoimmune disorders is associated with immunosuppression and myleosuppression. In the current study role of Zn on anti-Newcastle disease virus response and agranulocytes count of methotrexate and prednisolone treated rabbits. Thirty six healthy rabbits were randomly segregated into six groups (group I to VI) each containing six rabbits. Oil based Newcastle disease virus (NDV) vaccine was administered subcutaneously to rabbits of all the groups at day 0 and 21 and after one week, all the groups received Zn, (Zn + prednisolone), prednisolone, (Zn + methotrexate) methotrexate orally from day 7 to day 21, except the control. The serum antibody titer, total and differential leukocyte count were measured weekly for 6 weeks. The administration of zinc in combination with methotrexate showed same antibody titer as that of the control suggesting that Zn has ability to counteract the methotrexate-induced immunosuppression. However, Zn did not show any significant impact in combination with prednisolone (p<0.05). The results of the present study indicate that co-administration of Zn and methotrexate is beneficial in the activity of immune system.