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Objective: To investigate effects of Bletilla striata polysaccharide on expressions of nuclear factor kappa B（ NF-κB）/nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）/caspase-1 （caspase-1） pathway proteins and intestinal barrier damage in rats with ulcerative colitis（ UC）. Methods: UC model was induced by trinitrobenzene sulfonic acid（ TNBS）+ethanol, SD rats were randomly divided into: blank group, model group, Bletilla striata polysaccharide low（ 100 mg/kg）, medium（ 200 mg/kg）, high （400 mg/kg） doses groups and sulfasalazine positive group （0.67 g/kg）, and model was established in all groups except blank group. Bletilla striata polysaccharide low, middle, high groups and sulfasalazine group were given low, middle and high doses of Bletilla striata polysaccharide and sulfasalazine respectively by gavage, and rats in blank group and model group were administrated with 10 ml/kg saline by gavage for 2 weeks, once a day, and 12 hours after the last administration, general behavior of rats was observed and disease activity index （DAI） was scored; colonic tissues of rats were taken and histopathology was observed by hematoxylin-eosin staining; levels of myeloperoxidase （MPO）, IL-1β, tumor necrosis factor-α （TNF-α）, damage indexes of intestinal barrier function: diamine oxidase （DAO） and intestinal fatty acid binding protein （i-FABP） were detected by ELISA; Western blot was used to detect expressions of NF-κB, phosphorylated NF- κB p65 （p-NF- κB p65）, NLRP3, caspase-1 and cleaved caspase-1 proteins in colonic tissues. Results: Compared with blank group, rats in model group were emaciated, had loose stool, with pathological damages such as mucosal ulcer, hyperemia, dilatation and inflammatory cell infiltration, DAI score, contents of MPO, IL-1β and TNF- α, protein expressions of NF-κB, p-NF-κB p65, NLRP3, caspase-1 and cleaved caspase-1 were all increased （P<0.05）, and contents of DAO and i-FABP were decreased（ P<0.05）. Compared with model group, DAI score, degree of pathological damage of colon tissue, contents of MPO, IL-1β and TNF- α, p-NF- κB p65/NF- κB p65, NLRP3, caspase-1 and cleaved caspase-1 protein expressions were all decreased （P<0.05）, and contents of DAO and i-FABP were increased（ P<0.05）, which were in a dose-dependent manner, improvement effect of high dose of Bletilla striata polysaccharide was similar to sulfasalazine （P>0.05）. Conclusion: Bletilla striata polysaccharides can inhibit activation of NF-κB/NLRP3/caspase-1 pathway, reduce inflammation and intestinal barrier damage, and improve UC symptoms and intestinal mucosal damage. [ABSTRACT FROM AUTHOR]