AIM: To study the clinical characteristics of hyperuricemia (HUA) in ulcerative colitis (UC) patients and the role of uric acid in UC through clinical and animal experiments. METHODS: The clinical research included UC patients hospitalized for the first time in the Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine from April 2019 to April 2023. The patients were divided into two groups based on the presence of HUA, and the clinical data and laboratory indicators were collected. In the animal experiment, 24 SPF male C57BL/6J mice were randomly divided into ctrl group (Ctrl), model group (DSS), potassium oxonate group (PO), and uric acid group (UA). The body mass index, disease activity index (DAI) score, pathology, inflammation, and intestinal barrier function indexes were compared among groups. RESULTS: The clinical research showed that the prevalence of HUA in UC patients was 9% (41/455). Patients with HUA had a significantly higher proportion of male and BMI levels, and more extensive colonic types (P<0.05) than those without. In laboratory indicators, patients with HUA had significantly higher levels of C-reactive protein and triglyceride, and a substantially lower level of high-density lipoprotein cholesterol (P<0.05) than those without. The animal experiment found that compared with the Ctrl group, the DSS group significantly decreased body weight, shortened colon length, and increased DAI score. Pathological results showed a large number of inflammatory infiltrations and significant damage to the crypt structure. Moreover, the expression level of IL-6 in colon tissue was significantly increased, and the expression levels of MUC-2 and ZO-1 were significantly decreased (P<0.05). Compared with the DSS group, both the PO group and UA group could aggravate the above symptoms, indicating that uric acid has a significant pro-inflammatory effect on DSS-induced UC model mice. CONCLUSION: HUA is not uncommon in UC patients and such patients have a wider range of lesions and more severe inflammation. The mechanism may be that high uric acid aggravates inflammation.