Thus, in the present study, we used early weaned piglets infected by ETEC K88 as model to evaluate the morphologic alterations in the intestinal mucosa, and investigate the effect VIP on intestinal mucosal immunity and bacterial community, and the role of TLRs/myeloid differentiation factor 88 (MyD88)/NF-κB and (or) TLRs/MyD88/MAPK in modulatory effect of VIP on intestinal mucosal immune function under infection by ETEC K88. Here, VIP is linked to infection.