Background: Ulcerative Colitis is idiopathic inflammation and ulceration of colonicmucosa. Although several drugs are currently used for treatment of UC such asAminosalicylate, Corticosteroids and Immunosuppressive agents, and Biologicalagents such as TNFα inhibitors, they alleviate the symptoms but do not cure thedisease and have some limitations owing to their severe side effects. Consequently,looking for new agents that are equally or more effective and cause fewer sideeffects are needed. Interesting in natural products and herbs as alternativetherapeutic agents for UC has been accelerated in last decades. Myrrh has been usedas a medicinal herb for thousands of years, for treatment of many inflammatoryconditions in the body including gastrointestinal inflammation. it contain manybioactive constituents such as, flavonoids, triterpenes, commiphoric acid and others.Modern pharmacological studies have demonstrated that myrrh extract has antiinflammatory,antiseptic, antibacterial, antiparasitic, astringent, mucosalCytoprotective, and antioxidant effects.The aim of this work: was to elucidate the possible protective and therapeuticeffects of alcoholic myrrh extract on acetic acid‐induced Ulcerative colitis in ratmodel.Methods: In the present work, eighty six rats were randomized into six maingroups. Normal control group, divided in to two subgroups (1A,1B), Acetic Acidcontrol group, divided in to two subgroups (2A, 2B), vehicle group (olive oil), dividedin to two subgroups (3A,3B), positive control group ( SPZ), divided in to twosubgroups (4A,4B), prophylactic (pre colitis) tested group, divided into threesubgroups ( 5.A, AME 150mg\kg; 5.B, AME 500mg\kg and 5.C, both AME 150mg\kgand PSZ 500mg\kg) and therapeutic (post colitis) tested group, divided into threesubgroups ( 6.A,B,C similar to group 5 above). Each subgroup contained six rats, eachrat in each group (except normal control group which received normal saline insteadof AA) subjected to intrarectal instillation of single dose of 2ml 4% AA, and otherdrugs were administered daily by gastric gavage started 3 days before induction inpre colitis groups and 2 days after induction in post colitis groups and continued for 7days. the colonic mucosal damage induced by AA was assessed by physicalparameters including DAI, colon weight to length ratio measurement; gross andmicroscopic histopathological studies and biochemical measurement of inflammatorymarkers including CRP and T.L.C and colonic tissue level of TNFα and MPO activity Result: the study showed that in colitis group, all rats developed increasing indisease activity index and colon weight/length ratio, gross colonic mucosa showedsignificant ulceration, edema, hemorrhages. Histopathological sections showedsuperficial erosion of mucosal epithelial cells, epithelial necrosis, diffuseinflammatory cells infiltration in lamina propria, cryptitis , mucosal and submucosaledema. Colonic tissue MPO and TNFα content and serum CRP were significantlyincreased. Administration of AME, produced significant and dose‐dependentamelioration of AA induced changes. it improved the DAI, reduced in colon weight tolength ratio , attenuated of colonic mucosal macroscopic changes (decreased colonicmucosal ulceration, edema, and hemorrhages), amelioration of microscopic changes(restoration of surface epithelium, increase in number of goblet cells, reduced cryptsdistortion as well as reduced inflammatory cellular infiltrate in lamina propria) andreversed the biochemical changes including colonic tissue MPO activity, TNFα andserum CRP near to the normal level, in both prophylactic and therapeutic groups.AME in a dose of 500mg\kg is effective as SPZ. However, combination of both AMEand SPZ showed greater efficacy than each treatment alone. Olive oil didn't showany protective or curative effect on AA induced colitis.Conclusion, the present investigation elucidates that myrrh extract has protectiveand therapeutic beneficial effects in the amelioration of acetic acid inducedexperimental colitis, which could be related to its various phytochemical constituentsthat possess potent anti‐inflammatory, antioxidant, antiseptic and mucosalCytoprotective effects.