The ability to improve the efficacy of an inactivated Newcastle disease vaccine by addition of immunomodulator as propioni- bacterium and lipopolysaccharide (IM-104) was studied. Chickens were divided into three groups, one received inactivated Newcastle vaccine containing the IM-104, second group received vaccine alone and third group of chickens was left without vaccination as control. Blood samples were collected 3 days post vaccination, and weekly till four weeks for estimation of the effect of (IM-104) on T-lymphocyte transformation (cellular immune response). Sero-conversion for sera at weekly intervals was done to evaluate the immune response using HI test and ELISA. Challenge test was carried out on 3^rd and 6^th week post vaccination for evaluation of protective efficacy of these vaccines. The results obtained revealed that (IM-104) that contain 2 extraction of E. coli lipopolysaccharide and propioni-bacterium plays roles in stimulating both T-lymphocyte and macrophage to release different types of interleukin and consequently released immunoglobulins. Also, stimulate non-specific resistance to viral infection. The results obtained by challenge test run in parallel with that of serological test.