Bacterial disease still has serious problem in the intensive poultry production. In the recent years, particular concern has been raised by high incidence of poultry infections by E. coli. Analyses of antibacterial properties of essential oils have been carried out by range of researches. This experiment aimed to study the effect of immunomodulators on the immunogenicity of vaccine E. coli O78. In this study 250 broiler chickens were used. They were divided into 5 separated groups all groups vaccinated with E. coli O78 cebel coarse spray vaccine, except control group, 2 groups treated with immunomodulators, 3 groups challenged with untyped E. coli strain, all chickens housed in separated anavar. First group was control, 2nd group was vaccinated only, 3rd group was vaccinated and challenged, 4th group was vaccinated and received immunomodulators and 5th group was vaccinated, received immunomodulators and challenged. All chickens were observed daily food consumption, weight gained mortality rate, lesion, bioavailability, and weekly collected blood samples from 2-5 birds. The results were summarized as follows; immunomodulators have positive effect on B.W.G, decreased mortality and morbidity rate. The challenge enhanced the effect of E. coli O78 vaccine and there was marked improvement in bioavailability, B.W.G and immune defense against bacterial and respiratory diseases. Also, immunomodulators increased immunogenicity against bacterial disease through enhancing immune response system, and had synergistic effect with vaccination against E. coli.