Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1Formula: see text (HIF-1Formula: see text). In addition, the release of prostaglandin E and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1Formula: see text expressions in the tumor necrosis factor-Formula: see text stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of IFormula: see textB and the translocation of the nuclear factor-Formula: see textB (NF-Formula: see textB). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-Formula: see textB transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.