TNBS-ethanol administration is characterized by Th1-driven inflammation, and has primarily been regarded as a model for CD. The clinical features include weight loss and bloody diarrhea, while morphologically the model is characterized by mucosal, subMepiroxol mucosal and transmural inflammation. Consequently, the model has been used to investigate the role and 3,4,5-Trimethoxyphenylacetic acid mechanistic action of drugs including 5-aminosalisylic acid, steroids and anti-tumor necrosis factor in IBD. The administration and doses of TNBS differ significantly between studies; the methodology is inconsistent and no standardized protocol exists. Both TNBS-colitis and IBD include disturbances in basic physiological processes like immune activation, metabolism and mucosal repair. Microbial regulation of TLRs and induction of an inflammatory response is accompanied by regulation of proand anti-inflammatory cytokines and the shaping of the intestinal immune response. Down-regulation of the peroxisome proliferator-activated receptor gamma involved in the regulation of fatty acid metabolism and inflammation, has been demonstrated in IBD and is associated with maintenance of defensin expression. The cellular Prion protein is expressed in brain and various extra cerebral tissues including neuroendocrine cells and lymphoid tissue of the gut. PrPc can have an anti-inflammatory effect in the colon. We report the development and characterization of TNBScolitis in rats using colonoscopy and temporal gene expression profiling. The aim was to standardize TNBS administration to achieve a moderate inflammation. Achieving a moderate colitis allowed for the study of epithelial alterations upon mucosal damage, while temporal gene expression profiling identified longitudinal transcriptomic changes that were associated with these abnormalities. We further aimed to compare the genomewide changes in TNBS-colitis to a human transcriptome to determine whether TNBS at this dose was an appropriate model for IBD. TNBS-colitis is widely used as a model for IBD. However, its resemblance to human disease has not been thoroughly explored. TNBS-colitis in rats was originally described as a model for induction of long lasting inflammation and ulceration of the rat colon, and the reproducibility was emphasized. The reproducibility and duration/chronicity of inflammation has, however, been subject to debate. In the current study, we standardized the protocol for induction of moderate TNBS-colitis in Sprague Dawley rats and evaluated temporal changes in gene expression profiles and biological pathways after the induction of colitis. Importantly, we quantitatively assessed concordance of the TNBS-colitis and IBD transcriptomes. Doses and concentrations of TNBS used in previous studies differ markedly and no standardized protocol has been generally developed. We therefore aimed to optimize the method to achieve a reproducible moderate colitis. High concentrations of TNBS, administered in small volumes induced a localized severe inflammation resulting in deep colonic ulcerations, coprostasis, stenoses and ileus. Milder inflammation and more wide spread inflammation was achieved with lower TNBS concentrations in a larger total volume. A TNBS concentration of 30 mg/ml in a total volume of 0.6 ml resulted in a moderate inflammation involving most of the left colon. However, despite the use of a standardized protocol, a slight inter-individual dissimilarity in the extension and degree of inflammation was seen.