The complex interaction of genetic, microbial and environmental factors may result in continuous activation of the mucosal immune system leading to inflammatory bowel disease (IBD). Most current treatments for IBD involve altering or suppressing the aberrant immune response, however the role of the intestinal microbiota in the pathophysiology of IBD is becoming more evident. The epithelial layer is essential for the proper functioning of the gastrointestinal tract and its increased permeability to the luminal antigens may lead to the inflammatory processes and mucosal damage observed in IBD. Factors affecting the efficacy of the epithelial barrier include: presence of the pathogenic bacteria (e.g. Helicobacter spp.), presence of probiotics, availability of selected nutrients and others. The defective function of the mucosal barrier might facilitate the contact of bacterial antigens and adjuvants with innate and adaptive immune cells to generate prolonged inflammatory responses. This review will briefly describe the complex structure of the epithelial barrier in the context of bacterial-mucosal interactions observed in human IBD and mouse models of colitis.