TNF-like Weak Inducer of Apoptosis (TWEAK) and Fn14 are TNF superfamily members that were reported to be elevated in colonic samples of UC patients. However, the precise role of TWEAK/Fn14 in intestinal inflammation is still not fully elucidated. The aim of this study was to determine the effects of genetic deletion of TWEAK/Fn14 in a model of CD-like ileitis (SAMP mice) as well as to analyze their levels in IBD patients compared to healthy controls (HC).