Introduction: Ulcerative colitis is an inflammatory disease that affects the colon and causes a number of pathological changes in the colon mucosa. Mucosal changes are one of the risk factors in the development of colon cancer. The disease has a chronic course and it is characterized by periods of severe manifestations and a remission state. Some of the main symptoms are bloody diarrhea, nausea, headache, and weight loss. Currently used treatments of ulcerative colitis are unsatisfactory, while natural bioactive compounds like flavonoides are considered to be emerging therapeutic agents. Luteolin is a natural compound with beneficial effects on a variety of diseases, however, its effect on ulcerative colitis has been poorly studied. Luteolin is one of the members of a large group of flavonoids, and is distinguished by its antitumor, anti-inflammatory, antioxidant, and antiapoptotic effect in many diseases. Aim: using an experimental model of ulcerative colitis investigate the effect of luteolin on the development and intensity of ulcerative colitis and the process of apoptosis. Material and methods: The ulcerative colitis was induced by the administration of 3% dextran sulfate sodium salt (DSS) in drinking water for seven days. To investigate the effect of luteolin on the development of colitis two doses of luteolin are administrated between day 3 and day 7 of the experiment period, orally. During the development of colitis, clinical changes were monitored as well as the degree of damage of the colon tissue by histopathological analysis. The expression of the investigated proteins was determined by the Western blot method and immunohistochemically. Results: Luteolin attenuated symptoms of DSS-induced colitis in mice, ameliorated colon tissue damage, and reduced inflammation. Luteolin significantly reduced the expression of nuclear factor-kappa of subunit p65 and proapoptotic proteins. Conclusions: The results confirmed the anti-inflammatory and anti-apoptotic effects of luteolin. This suggested that luteolin can be used as a novel therapeutic candidate in the treatment of ulcerative colitis or could be used as a supplement to existing therapy.