Mongolian gerbils are used as biomedical research models for a variety of diseases and are in some cases suited better than other rodents for basic research and therapeutic studies. The aim of this study was to establish and characterize a dextran sulphate sodium (DSS)-induced model in gerbils for the human inflammatory bowel disease (IBD) and to utilize them for a therapeutic study in vivo. Four concentrations (0.5%, 1%, 2% and 4%) of DSS were administered via drinking water for 7 days; based on these results, a concentration of 3% DSS was given for 9 days in a second approach. Fluid uptake and general clinical condition were assessed daily using a clinical score. Caecum and colon were scored histologically. Fluid uptake was affected by addition of DSS to the drinking water. First clinical symptoms were observed at day 4 of DSS treatment with a considerable increase in clinical score parameters only in gerbils receiving 2% or 4% DSS. Histologically, ulceration and inflammation were observed predominantly in the caecum of gerbils treated with at least 1% DSS; reproducible inflammation in the colon required at least 2% DSS. Using 3% DSS for 9 days, considerably more inflammation was induced in the colon, comparable with lesions usually observed in the mouse model. Using an optimized protocol, DSS treatment induces reproducibly typhlocolitis in Mongolian gerbils, rendering them as a useful model for IBD.