Echinacoside (ECH) is a major bioactive phenyethanoids in medicinal herba Cistanche and has been reported to have antiinflammatory activity and beneficial effect on wound healing in many experimental studies. This study was to test the efficacy of ECH-enriched extract of Cistanche tubulosa in the treatment of dextran sulphate sodium (DSS)-induced colitis, a preclinical model of ulcerative colitis. Oral administration of ECH extract significantly suppresses the development of acute colitis, indicated by lowering disease activity index (p < 0.0001, n = 8) and preventing colonic damage (p = 0.0336). Histological examinations showed that ECH extract treatment protected intestinal epithelium from inflammatory injury (p = 0.0249) but had less effect on inflammatory cellular infiltration (p = 0.1753). The beneficial effect of ECH extract treatment was associated with upregulation of transforming growth factor (TGF)-β1 as well as with an increase in the number of Ki67+ proliferating cells in diseased colons (p < 0.0001). In cultured MODE-K cells, the addition of ECH extract enhanced in vitro wound healing that depended on TGF-β1 expression. These data suggest that ECH extract possesses a greater efficacy in preventing DSS-induced colitis in mice, implying the potential of ECH or its derivatives for clinically treating inflammatory bowel disease. Copyright © 2013 John Wiley & Sons, Ltd.