Objective To investigate the anti-inflammatory effect of LREE on a rat model of ulcerative colitis (UC) induced by TNBS. Methods Thirty-six male Sprague-Dawley rats were randomly divided into 6 groups: the normal control group (NC), model control group ( TNBS), positive control group ( SASP), and WY-L, WY-M, and WY-H groups. The rat model of UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the Linderae Radix ethanol extracts (LREE) were given by intragastric administration for 9 days. During the experimental period, disease symptoms, including body weight and stool features, and the colon histomorphology of UC model rats were observed. The activity of myeloperoxidase (MPO) in the colon was measured, the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined, and the proportion of regulatory T cells (Treg) and other lymphocyte subsets in the peripheral blood was detected by flow cytometry. Results The result showed that all three doses of LREE could significantly improve the symptoms of hematochezia and weight loss in UC model rats and reduce the serum levels of IL-6 ( P< 0. 05). Furthermore, LREE reduced the weight and length of the colon and rectum and improved the macroscopic changes, such as intestinal mucosal congestion and intestinal wall shortening and thickening, and histomorphological changes, including intestinal epithelial cell injury and immune cell infiltration. Additionally, low and middle doses reduced the serum level of TNF-α and activity of MPO in the colon (P<0. 05) and increased the proportion of Treg cells in the peripheral blood of model rats. Conclusions These findings suggested that LREE exerted anti-UC effects on the rat model induced by TNBS and that the mechanism might be associated with the inhibition of inflammatory cytokines, such as IL-6 and TNF-α.