Abstract: In order to explore the effect of Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron in preventing dextran sodium sulfate（DSS）-induced ulcerative colitis（UC） in rats, 64 SD rats were randomly divided into eight groups, namely the blank control group, the model group, Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron low（50 mg/kg）, medium（100 mg/kg） and high（200 mg/kg） groups. Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron dosage groups were given 1 mL of Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron by gavage of 50, 100, 200 mg/kg each at low, medium and high doses; one time a day, continuous gastric gavage for 14 days. The blank control group and the model group were given an equal volume of normal saline. From the 15 th day, the gavage was stopped, except for the blank control group, all the drinking water of the remaining groups was replaced with 4.5% DSS-containing aqueous solution, which could be drunk for seven days; a rat model of ulcerative colitis was established. At the end of the intervention, the body weight and colon length of rats were measured, and disease activity index（DAI） scoring was carried out; the histopathological changes of colon were observed by H.E. staining; the inflammatory factors interleukin（IL）-1β, IL-6 and tumor necrosis factor α（TNF-α） in serum were determined by ELISA; fluorescence quantitative PCR was used to detect the expression of tight junction protein-related genes ZO-1, Occludin and Claudin-1 mRNA in colonic tissues, and the relative levels of 16 S RNA gene of intestinal flora Mucispirillum schaedleri, Faecalibacterium prausnitzii, Escherichia coli, Lactobacillus and Bifidobacterium. The results showed that compared with the blank control group, the rats in the model group started to lose weight continuously since the 18 th day of the test, and the colon length was shortened very significantly（P＜0.01）; the DAI score increased and the colon lesions were severe; the serum levels of IL-1β, IL-6 and TNF-α were increased very significantly（P＜0.01）; the relative expression of tight junction proteins ZO-1, Occludin and Claudin-1 mRNA in colon tissues was very significantly decreased（P＜0.01）; the relative levels of 16 S RNA gene of intestinal flora Mucispirillum schaedleri and Escherichia coli were very significantly increased（P＜0.01）; and the relative levels of 16 S RNA gene of Faecalibacterium prausnitzii, Lactobacillus and Bifidobacterium were very significantly decreased（P＜0.01）. Compared with the model group, on the 18 th and 21 st day of the test, the rats in the Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron dose groups had regained body weight, and had less shortened colon length; DAI scores, and the serum levels of IL-1β, IL-6, TNF-α were significantly or very significantly lower（P＜0.05 or P＜0.01）; the relative expression of mRNA of tight junction proteins ZO-1, Occludin and Claudin-1 in Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron medium and high groups was increased. In the Agaricus blazei polysaccharide dose groups, the relative expression of 16 S rRNA gene of Faecalibacterium prausnitzii, Lactobacillus and Bifidobacterium was significantly or very significantly increased（P＜0.05 or P＜0.01）, and the relative expression of 16 S rRNA gene of Mucispirillum schaedleri and Escherichia coli was significantly or very significantly decreased（P＜0.05 or P＜0.01）. When the concentration of iron agaricus polysaccharide increased, the relative expression of 16 S rRNA gene of Mucispirillum schaedleri and Escherichia coli showed a decrease and then an increase, and was significantly higher at the high concentration than that in the medium dose group（P＜0.05）, and with the increase of the concentration of Agaricus blazei polysaccharide iron, the relative expression of 16 S rRNA gene of Bifidobacterium and Lactobacillus showed a trend of increasing and then decreasing. The results suggested that both Agaricus blazei polysaccharide and Agaricus blazei polysaccharide iron had preventive effect on DSS-induced acute UC in rats, but Agaricus blazei polysaccharide iron showed deficiency in correcting intestinal flora, which inferred that further study would be needed for its use as a preventive drug for colitis.