In the current study, the ameliorating effect of total polyphenol from Houttuynia cordataon mice with ulcerative colitis was studied. 50 male KM mice were randomly divided into control group, modelgroup, low-, medium- and high-dose groups of polyphenol in Houttuynia cordata. The model group was induced by administering 3.5% dextran sodium sulphate (DSS) for 9 days. On third day, the polyphenol groups were infused to stomach after DSS administration for another 10 days. The changes of mice body weight, colonic histomorphology and the disease activity index (DAI) of each group were observed. The levels of TNF-α, IL-1β, IL-6, IFN-γ in serum were detected by ELISA. The expressions of aspartate aminotransferase (AST), aspartate transaminase (ALT), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Compared with the DSS group, polyphenol groups significantly reduced symptoms with bloody stool. Disease activity index (DAI) decreased to 29.83%, 46.45% and 54.82%, respectively. The mice colon increased to 8.35 cm (in low dose group), 9.53 cm (in medium dose group), and 10.87 cm (in high dose group) on average. Also, treatment with polyphenol considerably the ALT and AST level and the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were decreased. These results demonstrate that polyphenol in Houttuynia cordata has an ameliorative effect on colonic damage, and decrease the level of serum proinflammatory factor. The mechanism may be related to inhibiting the activation of NF-κB.