Eradication of infectious disease is our global health challenge. After encountering intestinal infection with a bacterial pathogen, the host defense program is initiated by local antigen-presenting cells (APCs) that eliminate invading pathogens by phagocytosis and establish localized inflammation by secreting cytokines and chemokines. These pathogen-experienced APCs migrate to the mesenteric lymph nodes, where host immune responses are precisely orchestrated. Initiation and regulation of this defense program appear to be largely dependent on innate immunity which is antigen non-specific and provides a rapid defense against broader targets. On the other hand, many bacterial enteropathogens have evoked abilities to modify the host defense program to their advantage. Therefore, better understanding of the host-pathogen interactions is essential to establish effective eradication strategies for enteric infectious diseases. In this review, we will discuss the current understanding of innate immune regulation of the host defense mechanisms against intestinal infection by bacterial pathogens.