BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by the overproduction of reactive oxygen species (ROS) and the release of inflammatory mediators. Dihydroartemisinin (DHA) is a semi-synthetic active metabolite of artemisinin that has anti-inflammatory, antioxidant, and anti-fibrotic properties. OBJECTIVE: This study aimed to assess the therapeutic benefits of DHA on acetic acid(AA) -induced UC in rats, with particular emphasis on its anti-inflammatory effects and its influence on NFκB/TNF-α/RIPK1 necroptotic pathways. METHODS: Eighteen rats were allocated into control, acetic acid-induced colitis (AA), and DHA-treated (AA+DHA) groups. Colitis was caused by rectal instillation of 5 % acetic acid. DHA was supplied via intraperitoneal injection. Histological, biochemical studies of oxidative stress, inflammatory and anti-inflammatory mediators, Western blotting for TNF-α, RIPK1, and caspase 3, and immunohistochemical assessment of NFκB, TNF-α, and RIPK1, were conducted. RESULTS: DHA treatment markedly diminished macroscopic damage, disease activity index, histopathology scores, and malondialdehyde (MDA) levels, enhancing glutathione (GSH) levels. Additionally, DHA decreased serum TNF-α and IL-6 and increased IL-10. Western blotting and immunohistochemistry investigations validated the reduced expression of TNF-α, RIPK1, and caspase 3 in DHA-treated rats. CONCLUSION: DHA demonstrates protective properties against acetic acid-induced UC by decreasing oxidative stress and inflammation, modifying TNF-α activity to regulate apoptotic and necroptotic pathways. So, DHA may be a favorable therapeutic alternative for the management of ulcerative colitis.