Tumor necrosis factor (TNF) plays a pivotal role in the pathogenesis of Crohn's disease (CD). However, little is known about the role of TNF receptors (TNF‐R) in this disease. Here, we found that TNF‐R2 (in contrast to TNF‐R1) was significantly up‐regulated on lamina propria and peripheral blood T cells in CD compared to control patients. To directly test the functional role of TNF‐R2 in Th1‐mediated experimental colitis in vivo, we took advantage of transgenic animals overexpressing TNF‐R2 in T cells. Reconstitution of SCID mice with CD4⁺ CD62L⁺ T cells from TNF‐R2 transgenic mice led to an earlier wasting syndrome, a more severe colitis and augmented Th1 cytokine production than reconstitution with cells from wild‐type littermates. In addition, TUNEL staining revealed a significantly decreased apoptosis rate of lamina propria mononuclear cells in mice reconstituted with TNF‐R2 transgenic T cells compared to mice reconstituted with wild‐type T cells. In summary, our data suggest a critical regulatory role of TNF‐R2 signaling for disease exacerbation in Th1‐mediated chronic colitis. Taken together with the increased expression of TNF‐R2 inCD, selective targeting of TNF‐R2 signaling thus emerges as a potentially novel approach to the treatment of CD.