By its antioxidant effect, molecular hydrogen gas (H-2) was reported to protect organs from tissue damage induced by ischemia reperfusion. To evaluate its anti-inflammatory effects, we established a mouse model of human inflammatory bowel disease (IBD) by supplying mice with water containing (1) dextran sodium sulfate (DSS) (5%), (2) DSS (5%) and H-2, or (3) H-2 only ad libitum up to 7 days. At day-7, DSS-induced pathogenic outcomes including, loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of IL-12. TNF-alpha and IL-1 beta in colon lesion, were significantly suppressed by the addition of H-2 to DSS solution. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H-2. Therefore, the present study indicated that H-2 can prevent the development of DSS-induced colitis in mice. (C) 2009 Elsevier Inc. All rights reserved.