Abstract: OBJECTIVE To study the mechanism of Antrodia camphorata polysaccharide regulate mouse chronic colitis via intestinal mucosal infiltration of Th9 and its cell factor IL-9. METHODS The chronic colitis model was established by dextran sulfate sodium (DSS). Set the normal group, the model group, the positive control group (anti IL-9 antibody injection group), the Antrodia camphorata polysaccharide group (20 mg·kg^-1 Antrodia camphorata polysaccharide). Activity in mice within one month was comprehensive evaluated by DAI score. Body weight changes of mice in one month were detected. Flow cytometry was used to detect the proportion of CD4+IL-9+T cells in the mononuclear cells of the peripheral blood and intestinal mucosa. The expression of IL-9, TGF-β and IL-4 in peripheral blood and intestinal mucosa were detected by ELISA. IL-9, TGF-β, Smad3 and IL-4 expression in mouse mucosa were detected by real-time quantitative PCR. HE staining was used to observe the pathological changes of colon tissue in mice. RESULTS DSS could induce chronic colitis in mice, DAI results showed that the activity of mice in the model group decreased significantly and therer is a significant decreased in DAI score in the prognosis of polysaccharides (P<0.05). The ratio of Th9 in the peripheral blood and intestinal lamina propria of model mice was significantly higher than that in the normal group (P<0.05). The expressions of IL-9, TGF-β, IL-4 protein and mRNA in peripheral blood and intestinal mucosa were also increased significantly (P<0.05). In the positive control group and the Antrodia camphorata polysaccharide group, the ratio of Th9 in the peripheral blood and intestinal lamina propria was lower than that in the model group after intervention (P<0.05). The expressions of IL-9 TGF-β, IL-4 protein and mRNA in peripheral blood and intestinal mucosa were also declined significantly (P<0.05). The pathological changes of colon were obviously improved by HE staining. CONCLUSION Antrodia camphorata polysaccharide can improve chronic colitis in mice via intestinal mucosal infiltration of Th9 and its cell factor IL-9. The mechanism is related to immune regulation and anti-inflammatory reaction