Ulcerative colitis (UC) is a chronic health condition characterised by inflammation and ulcer formation in the colon and rectum. Although Chlorella vulgaris (C.V) possesses anti-inflammatory properties and additional therapeutic advantages, its efficacy in managing colitis has not been researched. Our research aims to examine the anti-colitis properties of Chlorella vulgaris using a colitis model in rats induced by acetic acid. Sixty male Wistar rats (150-170 g) were randomly distributed into six groups, including control group, acetic acid (received 2 ml per animal of 4% acetic acid transrectal single dose on the 15th day by (pediatric plastic catheter), sulfasalazine (100mg/kg b.w), Chlorella vulgaris only (300 mg/kg b.w), Chlorella vulgaris (300 mg/kg b.w) with acetic acid, and Chlorella vulgaris at (300 mg/kg b.w) along with sulfasalazine (100 mg/kg b.w orally). Animals with induced colitis were sacrificed on the 7th day after induction, and whole blood was obtained for haematological analysis. Colons were removed for assessment of macroscopic and histological changes and for immunohistochemical and molecular analyses. Chlorella vulgaris treatment protects the colonic mucosa from inflammatory cell infiltration and destruction, profound erosive lesions, necrosis oedema, and loss of epithelial integrity. Moreover, administration of Chlorella vulgaris was associated with improved haematological parameters, macroscopic features, Malondialdehyde (MDA) and nitric oxide (NO) levels were lowered, whereas antioxidant/oxidant equilibrium was restored, as seen by increased catalase activity and decreased glutathione levels, inhibited inflammation by reducing NF-κB and apoptotic marker caspase-3 in colonic tissue, thus preventing apoptosis. In conclusion, Chlorella vulgaris effectively improves AA-induced UC in rats by reducing inflammation, apoptosis, and oxidative stress in colon tissue. Therefore, Chlorella vulgaris could be a suitable choice for UC therapy.