Immunomodulators provide an excellent approach as they mainly have fewer side effects than chemical drugs and have no affinity for creating microbial resistance. In order to investigate the Echinacea immunomodulatory effect on the immune response of broiler chickens,one hundred twenty (1-day-old) chicks of both sexes were randomly allocated into 2 dietary groups on floor pen (60 chicks/group), group1: Chicks were offered basal diets and kept as control group, group2: Chicks were offered basal diets supplemented with Echinacea purpurea (5gm/kg diet for 6 weeks). Evaluating the effects of Echinacea purpurea on growth performance, Serum Protein profile, total and differential leucocytic count, humeral immunity which was carried out by measuring antibody titer against Newcastle (ND) and (AIV) Avian Influenza vaccine, and on innate immunity which was carried by measuring some function of peripheral blood monocyte (PBM) as phagocytic activity, fungicidal activity, nitric oxide NO production and reactive oxygen species ROS production. Challenge test was carried out using virulent E. coli strain. The results revealed that, Echinacea improve growth performance, significantly increase antibody titer against ND and AIV vaccine as well as enhance the innate immunity by increasing the phagocytic activities, fungicidal activities, ROS production and nitric oxide production of monocytes. In challenge test,Echinacea reduce E. coli lesions, morbidity and mortality rate. Based on the results of this study, it could be concluded that growth performance and both humeral and innate immune responses of broiler chicks were improved by of dietary supplementation of Echinacea purpurea (5 g/kg diet), also it could protect broiler chickens from virulent E. coli infection.