Introduction: Intestinal colitis, also known as ulcerative colitis, is an inflammatory bowel disease characterized by long-term inflammation and ulcers in the gastrointestinal tract. It has been suggested that the mucosal expression of angiotensin II (AT-II) is increased in colitis. This study aimed to examine the potential therapeutic effects of combination therapy with Enalapril, an angiotensinconverting enzyme inhibitor, and sulfasalazine (SSZ) in a murine colitis model. Methods: Male C57BL/6 mice were divided into five groups: control group (distilled water), dextran sulphate sodium (DSS) group (colitis group) (1% DSS), SSZ group (positive control group) with 100 mg/kg/day, Enalapril alone group with 4 mg/kg/day, and Enalapril (4 mg/kg/day) + SSZ (100 mg/kg/day) group. Results: There was a significant reduction in the disease activity index among the mice receiving the combination of Enalapril and SSZ compared to the colitis group. Enalapril and SSZ treatment was associated with a lower reduction in colon length, decreased colon weight, spleen weight, and spleen-to-body weight in mice with colitis. Following DSS administration, Enalapril and SSZ also significantly decreased MDA levels, an oxidant marker, and increased total thiol, SOD, and CAT levels, as antioxidants. Additionally, mucosal damage, crypt loss, pathological changes, and inflammation scores decreased after treatment with Enalapril and SSZ in comparison with the colitis group. The combination of Enalapril and SSZ reduced colon collagen content and caused a decrease in fibrosis compared to the colitis group. Conclusion: The results of this study indicated that Enalapril alone and in combination with SSZ decreased inflammation and clinical symptoms of colitis induced by DSS.