Abstract: The in vitro effect of Nerium oleander (NO) aqueous leaf extract on humoral and phagocytic activity and in vivo cellular immune response were studied in rabbits. Treatment of rabbits with the extract at 75 mg kg 1 body weight subcutaneously not only diminished the production of antibodies, but also exerted an inhibition on delayed type hypersensitivity reaction and phagocytic activity, whereas treatment of rabbits at 50 and 25 mg kg 1 body weight subcutaneously caused stimulation of the immune system. These results suggest the NO aqueous leaf extract exerts a marked immunomodulatory effect on the rabbits, immune system.