In the present paper, the effect of Fumigaclavine C, a fungal metabolite, on experimental colitis was examined. Fumigaclavine C, when administered intraperitoneally once a day, significantly reduced the weight loss and mortality rate of mice with experimental colitis induced by intrarectally injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). This compound also markedly alleviated the macroscopic and microscopic appearances of colitis. Furthermore, Fumigaclavine C, given both in vivo and in vitro, showed a marked inhibition on the expression of several inflammatory cytokines, including IL-1beta, IL-2, IL-12alpha, IFN-gamma, TNF-alpha as well as MMP-9 in sacral lymph node cells, colonic patch lymphocytes and colitis tissues from the TNBS colitis mice. Meanwhile, the compound caused a dose-dependent reduction in IL-2 and IFN-gamma from the lymphocytes at the protein level and MMP-9 activity. These results suggest that Fumigaclavine C may alleviate experimental colitis mainly via down-regulating the production of Th1 cytokines and the activity of matrix metalloproteinase.