This study was designed to evaluate the effect of bacteriophage on macrophage-mediated inflammatory immune responses against intracellular pathogens. The intracellular survival of nonlysogenic, lysogenic Salmonella Typhimurium, and Listeria monocytogenes were evaluated in chicken macrophage HD11 cells treated with Salmonella bacteriophage P22 for 24 h at 37℃. The relative expression of inflammatory mediator-related genes (IL-1β, IL-6, IL-8, IL-10, LITAF, and iNOS) was estimated by using a qPCR. The production of inflammatory factors (IL-1β, IL-6, IL-8, IL-10, TNF-α, and NO) was determined by using ELISA kits. The numbers of invading nonlysogenic S. Typhimurium (ST), lysogenic S. Typhimurium (LY), and L. monocytogenes(LM) in HD11 cells were reduced by 0.90, 0.83, and 1.51 log units, respectively, after 1 h of infection at 37℃. The relative expression levels of inflammatory mediator-encoding genes (IL-8, IL-10, and iNOS) were increased in ST-and LM-infected chicken macrophage HD11 cells treated with P22. The level of NO production was increased to 26.8 μM at LM-infected HD11 cells treated with P22, which corresponded to the reduction of intracellular L. monocytogenes in HD11 cells. The results suggest that the bacteriophage P22 has the potential to reduce the numbers of intracellular pathogens, S. Typhimurium and L. monocytogenes. This study would provide valuable insights into the interaction between bacteriophages and macrophages and help to develop new strategies for enhancing the microbiological safety in poultry.