This work has been designed to investigate the protective potential of chicken egg yolk against salmonella infection using laboratory mice as a model. Mice that treated by egg yolk and experimentally infected with salmonella typhimurium showed survival rate of 92% and absence of infected bacteria compared to non treated group (20%). Histopathological examination revealed that treated group showed complete absence of histopathological changes in intestine and only few histopathological changes in liver and heart, while non treated group showed mucosal goblet cells formation with lymphoid follicular hyperplasia in serosa of intestine, significant infiltration of liver with leucocytic cells in hepatic tissue with necrotic changes and the heart showed leucocytic inflammatory cells infiltration in Between Bundles of degenerated cardiac muscles. So chicken egg yolk can be used in enhancing the immune system and could be effective in protecting different animal species against salmonella infection.