During intestinal inflammation epithelial barrier function is impaired contributing to diarrhea by a leak flux-mechanism and perpetuating mucosal inflammatory events by an increased luminal antigen uptake. Epithelial barrier strategies to counteract these functional defaults comprise several features, including the apical enterocyte membrane and the epithelial tight junction. This epithelial barrier can be affected by tight junction modulation, induction of epithelial apop-toses and the occurrence of epithelial gross lesions as well as by accelerated transcytotic anti-gen uptake through the enterocytes. In general, tight junction strands are reduced in Crohn’s disease (CD) as well as in ulcerative colitis (UC). In addition, strand breaks can appear. Several of the 24 claudins found in mam-malians can be affected in the IBD mucosa. Epithelial apoptotic rate has also been shown to be elevated, as the result of which focal lesions can occur already in early stages of UC. As far as regulatory influences are concerned Th1-cytokines like TNFalpha and interferon-gamma are important for CD, while Th2 responses are dominated by IL-13 and TNFalpha in UC. TNFalpha is known to induce tight junction alterations via different pathways including IP3/p-Akt, tyrosine kinase src and NFkappaB and can also induce apoptosis. IL-13 does stimulate epithelial apop-tosis as well as in particular up-regulates claudin-2. Together with an IL-13-dependent restitu-tion arrest this may explain why ulcer lesions are already early seen in ulcerative colitis but only in advanced stages of CD. In addition to tight junction discontinuities and epithelial gross le-sions, luminal antigen uptake occurs endocytotically. Endocytosis can be stimulated by inter-feron-gamma and/or TNFalpha. Therapeutically, anti-inflammatory remedies as e.g. TNFalpha antibodies improve active IBD and in parallel repair barrier function. Again, this is assumed to be due to reduced cytokine re-lease in active IBD, as result of immune cell apoptosis. Glucocorticoids can also affect immune cells in the mucosa and consequently interfere with tight junction regulation and apoptosis in-duction, as a result of which barrier dysfunction is improved in IBD. This action is usually inter-preted to be the direct result of the anti-inflammatory influence. However, glucocorticoids can also influence gene expression in enterocytes in favor of anti-diarrheal actions. So far, there is not much data support for a beneficial barrier role of glutamine in IBD, although it is an impor-tant metabolic fuel for enterocytes. In contrast, butyrate directly regulates claudin-2 expression and intensifies glucocorticoid effects supporting a beneficial role in IBD. Furthermore, nutritional food components can strengthen the epithelial barrier as e.g. flavonoids, since claudin-4 has e.g. been shown to be by up-regulation by quercetin. Finally, traditional drugs possess barrier protective effects via tight junction regulation as e.g. berberine.