The current study presents the establishment of a short-time-damage-model that could serve as an experimental test system to study the early progression of Ulcerative colitis (UC) pathogenesis and to evaluate novel therapeutic options. Mucosal inflammation was induced by an in situ perfusion of a defined segment of the small intestine with the sulfhydryl blocker iodoacetamide (IA). The IA-induced inflammation parameters could significantly improved by two clinically relevant UC therapeutics and the silicate Resormin. The molecular mechanisms by which Resormin exerted the beneficial effects were analysed in human intestinal epithelial cells. These results indicate that the therapeutic effect of the smectites in vitro and in the short-time-damage-model is due to the adhesion of pro-inflammatory cytokines and reactive metabolites.