The micro integral membrane protein (MIMP), the domain within the integral membrane protein of Lactobacillus plantarum CGMCC 1258, has been shown to adhere to mucin and antagonize the adhesion of enteroinvasive E. coli and enteropathogenic E. coli. To further characterize the functions of MIMP, we investigated its effects on the intestinal permeability, expression of tight junction (TJ) proteins and TJ ultrastructure in vitro and in vivo. We also determined the interaction between MIMP and dendritic cells (DCs). We observed that MIMP reduced intestinal permeability and restored the expression and distribution of TJ proteins in both NCM460 cell monolayers and in IL-10(-/-) mice. MIMP adhered to immature (i) DCs by binding to DC-SIGN, and induced DCs to produce anti-inflammatory cytokines and to mediate Th2 differentiation. Moreover, MIMP stimulated the expression of anti-inflammatory cytokines in colonic mucosa and attenuated colitis in IL-10(-/-) mice. In conclusion, MIMP is the main functional component of L. plantarum that contributes to its protective effects, and thus may be a potential therapeutic agent for intestinal diseases.