The intestinal mechanical barrier plays a key role in the pathogenesis of ulcerative colitis (UC). Our previous study showed keratin 1 (KRT1) was downregulated in UC, but the mechanism by which KRT1 affects the intestinal barrier remains unknown.To explore the mechanism of KRT1 in the intestinal barrier in UC.Colonic tissues were collected from 20 UC patients before and after mucosal healing (MH) and 15 healthy controls. The expression of KRT1 was measured by PCR, western blotting and immunohistochemistry (IHC). A dextran sulfate sodium (DSS)-induced colitis model was established in krt1 transgenic (TG) mice, and the mice were treated with methylprednisolone (MP) to explore the role of KRT1 in the intestinal barrier. Inflammation was evaluated through the DAI score, colon, spleen and H&E. The expression of KRT1 and tight junction (TJ) proteins in mouse was analysed by the same methods.The transcription and expression of KRT1 in UC was decreased and recovered after MH but did not reach the level of the healthy controls. Similar to the clinical results, the expression of krt1 was decreased in DSS-induced colitis and upregulated after MP. Moreover, the krt1 TG group exhibited less inflammation than wild-type (WT) group. The expression of Occludin and ZO-1 decreased after DSS induction, the decreases in Occludin and ZO-1 in the krt1 TG group were lower than WT group, which was significantly increased after MP, while the expression of Claudin-2 exhibited the opposite effect.Keratin 1 maintains the intestinal barrier by upregulating TJ proteins in UC.© 2021. The Genetics Society of Korea.