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Ulcerative Colitis (UC) is a chronic inflammatory condition of the large intestines. Although great advances have been made in the management of the disease with the introduction of immunomodulators and biological agents, the treatment of UC is still a challenge. So far, there are no definitive therapies for this condition. Statins are potent inhibitors of cholesterol biosynthesis, possess beneficial effects on primary and secondary prevention of coronary heart disease, and have high tolerability and safety. Furthermore, they may have potential roles in UC management due to their possible anti-inflammatory, immunomodulatory, and antioxidant activities. This systematic review aimed to gather information about the potential benefits of statins for managing UC, reducing inflammation and disease remission in animal models. A systematic search was performed in PubMed/MEDLINE, Scopus, Web of Science, and Virtual Health Library. The data were summarized in tables and critically analyzed. After the database search, 21 relevant studies were identified as eligible for this review. Preclinical studies using several colitis-induction protocols and various statins have shown numerous beneficial effects of these drugs on reducing disease activity, inflammatory profile, oxidative stress, and general clinical parameters of animals with UC. These studies revealed the potential of statins against the pathogenesis of UC. However, there are still important gaps regarding the molecular mechanisms of action of statins, leading to some contradictory results. Thus, more research on the molecular level to determine the roles of statins in colitis should be carried out to elucidate their mechanisms of action., (© 2022 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)