To observe the effects of moxibustion on tight junction proteins and serum inflammatory factors in wild-type and TRIM31 knockout (TRIM31-/-) ulcerative colitis (UC) model mice and explore the possibility of TRIM31 in reducing intestinal inflammation in UC by protecting the intestinal mucosal barrier，as well as the regulatory role of moxibustion.Methods:The UC model was induced in the wild-type and TRIM31-/-mice.Immunohistochemistry was used to detect the protein expression of TRIM31，Occludin，Claudin-1，and ZO-1 in colon tissues.RT-qPCR was used to detect the mRNA expression of TRIM31 in colon tissues.The serum levels of IL-1β，IL-13，IL-25，and IL-33 were detected by ELISA.Results:Moxibustion could resist colonic inflammation in wild-type UC mice，increase the protein and mRNA expression of TRIM31 and the expression of Occludin，Claudin-1，and ZO-1 in the colon，and reduce the concentrations of inflammatory factors IL-1β，IL-13，IL-25，and IL-33 in the serum.Compared with the wild-type mice，the TRIM31-/-mice showed aggravated colitis，decreased expression of Occludin，Claudin-1，and ZO-1，and increased serum concentrations of IL-1β and IL-13.Additionally，moxibustion could improve the colitis of TRIM31-/-UC mice，increase the expression of Occludin，Claudin-1，and ZO-1 in the colon，and reduce the serum concentrations of IL-1β，IL-13，IL-25，and IL-33.Conclusion:TRIM31 protein might serve as a key target of moxibustion in regulating the intestinal mucosal barrier in UC.The regulatory role of moxibustion on Occludin，Claudin-1，ZO-1，IL-1β，IL-13，IL-25，and IL-33 in TRIM31-/-mice was verified，which suggested that moxibustion presumedly participated in the protection of intestinal mucosal barrier in UC by virtue of its multi-target regulatory role.