Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by a controlled partial enzymatic hydrolysis of guar gum beans, has various physiological actions. The aim of the present study was to elucidate the beneficial effects of PHGG on colonic mucosal damage and on the inflammatory response in a dextran sulfate sodium (DSS) colitis model. After 2 weeks of prefeeding of PHGG, acute colitis was induced with 8% DSS in female BALB/c mice. Colonic mucosal inflammation was evaluated clinically, biochemically and histologically. Mucosal protein contents and mRNA levels of tumor necrosis factor-alpha (TNF-alpha) were determined by immunoassay and reverse transcription polymerase chain reaction. Disease activity scores determined by weight loss, stool consistency and blood in stool in DSS-treated mice were significantly lower in the PHGG-treated mice compared with the control mice. Shortening of the colon was significantly reversed by PHGG. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in PHGG-treated mice compared with the control mice. The increases in tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances after DSS administration were both significantly inhibited by pretreatment with PHGG. Partially hydrolyzed guar gum also inhibited increases in intestinal TNF-alpha protein and mRNA expression after DSS administration, respectively. These results suggest that chronic ingestion of PHGG prevents the development of DSS-induced colitis in mice via the inhibition of mucosal inflammatory response.