Background: Ulcerative colitis, a life-long recurrent relapsing-remitting disorder, is a type of debilitating chronic IBD of the colon that causes a superficial mucosal inflammation in a continuous fashion extending from the rectum to the more proximal colon, in varying extents. The hallmark symptoms of UC include bloody diarrhea with rectal urgency and tenesmus. Many UC patients experience extra intestinal manifestations (EIM) that involve multiple organs like erythema nodosum, pyoderma gangrenosum and arthritis. mucosa of the GIT is exposed to millions of antigens from the food, environment and microbiome. The epithelial barrier, covered by a mucinous layer, is the first-line defense of the mucosal immune system, because it provides physical separation between host immune cells and luminal microbes. Treatment of UC consists mainly of 5-aminosalycilates (5-ASAs), corticosteroids, immunosuppressive drugs, and monoclonal antibodies to TNF-α. Treatment success is dependent on several factors, such as use of the right drug for the right indication (induction vs maintenance), optimization of the dose, and maximization of drug adherence (non-adherence to mesalazine is associated with increased rates of relapse).Treatment should be tailored to disease activity (mild, moderate, severe) and the extent of colonic involvement (proctitis, left-sided colitis, or pancolitis). Agomelatine is an atypical antidepressant with a unique receptor profile, as a melatonin receptor (MT1 and MT2) agonist and a 5-HT2C receptor antagonist.