Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, which can suppress the inflammatory response. Recently, several studies indicated that activating AhR can inhibits inflammatory processes in the gut, and that AhR ligand may be a predicted drug to treat inflammatory bowel disease (IBD). In our previous study, indigo naturalis, a herbal medicine, considerably inhibited LPS-induced cytokine expression in cultured gastric epithelial cells and in intestine tissue of dextran sodium sulfate (DSS)-induced ulcerative colitis mice. Indigo, a major component of this medicine, is known to activate AhR. However, after the fractionation of Indigo naturalis, potent inhibitory effect on cytokine expression was obtained from water soluble fraction, which doesn’t contain indigo. This new active component of Indigo naturalis inhibited cytokine expression both in vitro and in vivo, as well as indigo, whereas it did not activate AhR with the same strength. Now, we are investigating the characteristics of the pharmacological effect of this new AhR ligand isolated from the water-soluble fraction. It might be a new AhR ligand, which can stimulate transrepressional activity of this receptor.