Background:Ulcerative colitis (UC) is a chronic inflammatory disease of large intestine. Overproduction of free radicals, lowered antioxidant capacity, inflammation and abnormal apoptosis are involved in its pathogenesis. Propranolol and carvedilol, βblockers with antioxidant and anti-inflammatory effects which may have a protective role in UC. The study aimed to evaluate and compare the effects of propranolol and carvedilol on UC development and to distinguish which of them have greater beneficial effect on experimentally-induced UC in male albino rats. Methods: Fifty male albino rats were randomly allocated to five groups with each group comprising eleven rats except control group composed of six rats. Group (1): control group, Group (2): ulcerative colitis group, Group (3): propranolol-pretreated (30 mg/kg/d), Group (4): carvedilol-pretreated (30 mg/kg/d) and Group (5): mesalazinepretreated (300 mg/kg/d). Treated groups received drugs by oral gavage for seven days before and three days after induction of colitis. UC was induced in groups 2 to 5 by intrarectal administration of 1ml of 4% Acetic Acid (AA), while group (1)received 1 ml of normal saline solution administered intrarectally instead. To estimate the severity of AAinduced UC and the effect of propranolol and carvedilol, the following parameters were measured: colon weight/length (W/L) ratio, colon weight/body weight (CW/BW) ratio, colonic malondialdehyde (MDA) and colonic markers of inflammation [tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB)] and macroscopic and microscopic scorings. Results:In UC group, colon W/L ratio, CW/BW ratio, macroscopic and microscopic scorings and colonic levels of MDA, TNF-α and NF-κBwere significantly increased. Pretreatment with propranolol, carvedilol and mesalazine significantly reduced these parameters when compared to UC group. However, colon W/L ratio, CW/BW ratio, macroscopic scoring of mucosal damage and colonic MDA, TNF-α and, NF-κB levels in carvedilol-pretreated group were significantly lower than propranolol-pretreated group. Conclusion:Both propranolol and carvedilol had a coloprotective effect againstAAinduced UC depending on their ability to decreases inflammation and oxidative stress state in rat colon; butcarvedilol had better effects than propranolol. Thus, carvedilol can be considered the β-blocker of benefit in patients with UC who have other co-existing diseases indicatingthe use of β-blockers.