Objective: Pachyman might reduce the intestinal dysfunction and inflammation. Therefore, in this study, we aimed to explore the effect of pachymic acid on repairing the intestine mucosal injury in mice. Materials and Methods: Male BALB/c mice were randomly divided into six groups: control group, trinitrobenzenesulfonic acid (TNBS)-induced group, pachymic acid (50, 100, and 200 mg/kg) groups, and mesalazine group. In addition to the mice in the control group, all mice in other groups were induced by TNBS, an inducer of colitis, to establish the intestine mucosal injury model. To study the effect of pachymic acid on the intestine mucosal injury in mice, we assessed the disease activity index (DAI) and the morphology colon specimen in mice. Histopathological examination was also used to access the effects of different concentrations of pachymic acid on the intestinal mucosal injury in mice. Enzyme-linked immunosorbent assay (ELISA) tests were performed to detect the level of glutathione (GSH), myeloperoxidase (MPO), (MDA), and pro-inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin (IL)-1 β, and IL-8) to evaluate the effect of pachymic acid on the biomarkers of oxidative stress and pro-inflammatory factors. At the in vitro level, the human colon carcinoma cells (Caco-2) were induced by TNBS to establish the in vitro intestinal mucosal injury model. After treatment with the pachymic acid, the cell viability was examined by methyl thiazolyl tetrazolium assay, and the cell apoptosis was detected by flow cytometric analysis. The expression levels of apoptosis-related proteins were analyzed by Western blot analysis. Meanwhile, the secretion level of TNF-α, IL-1 β, and IL-8 in the supernatant of Caco-2 cells was detected by ELISA kits. Results: Pachymic acid was found to reduce the DAI of intestine mucosal injury in treated mice and improved the hyperemia, edema, and necrosis in intestinal mucosal tissue. Pachymic acid decreased the secretion levels of pro-inflammatory factors TNF-α, IL-1 β, and IL-8, as well as the oxidative stress markers, MPO and MDA. In contrast, the serum levels of GSH were found to be increased. After being challenged by TNBS, the cell viability of Caco-2 cells was inhibited, while after treated with pachymic acid, inhibitory effect was partially blocked. Similarly, the TNBS-induced Caco-2 cells' apoptosis was abolished by pachymic acid. Conclusion: Pachymic acid repaired the intestine mucosal injury and attenuated inflammatory response in experimental mice. It provides an alternative therapeutic strategy for intestine mucosal injury and highlights the protective effects of traditional Chinese medicine in these diseases.