Recent studies have suggested a critical role of TNFR2 signaling associated with NF-kappaB activation in the pathogenesis of Crohn's disease. Triptolide, an extract from Tripterygium wilfordii Hook, has both anti-immune and anti-inflammatory effects. In this study, we evaluated its possible therapeutic effects on colitis in interleukin-10 deficient mice, a murine model of Crohn's disease. Triptolide was administered to IL-10(-/-) mice intraperitoneally every other day for 8 weeks. The severity of colitis in IL-10(-/-) mice was obviously reduced after triptolide treatment, with a reduction in the numbers of CD4+ T cells and macrophages in lamina propria. Triptolide also significantly decreased the production of TNF-alpha and IFN-gamma in colon. Furthermore, triptolide suppressed TNFR2 expression and NF-kappaB activation in colon of IL-10(-/-) mice. These data suggested that triptolide could ameliorate Th1-mediated chronic colitis and disordered immune state in IL-10(-/-) mice. A possible mechanism could be inhibiting TNF-alpha/TNFR2 signal pathway.