Ulcerative colitis (UC) manifests as chronic inflammation of the colon. The bowel inflammation is due to alteration in the immune response to gut micro flora, oxidative stress and hereditary genetic factors. Leaf extract of papaya Carica papaya Linn. contain vitamin A, C, alkaloids, saponins, glycosides, tannins and flavonoids which have antispasmodic, analgesic, antibacterial and antioxidant properties. The main aim of the study was to detect the efficacy of Carica papaya leaf extract (PLE) on ulcerative colitis in Wistar Albino rats with objectives to explore the possible mechanism involved in its efficacy and to look for prebiotic activity. The project was initiated after the approval of Institutional Animal Ethics Committee. Thirty adult Wistar rats were randomly assigned into seven groups of six rats each. Group I-control, Group II-UC disease control, Group III-Disease with standard Sulfasalazine 100mg/kg, Group IV and Group V, UC disease model receiving PLE of 250mg/kg and 500 mg/kg respectively. Ulcerative colitis was not induced in Group VI and Group VII which received PLE of 500mg/kg and 700 mg/kg respectively. All the drugs were administered orally for 15 days. UC was induced by acetic acid on the 8th day. Blood sample was collected for biochemical analysis for antioxidant levels. Histopathological analysis of distal colon was performed to look for inflammatory features. Microbial analysis was done for group VI and group VII. There was significant reduction in body weight in UC induced groups when compared to control. The weight loss in Group IV and V (PE1 and PE2) was not as extreme as seen in the UC alone group. The treatment groups IV and V showed significant increase in protein levels, increased catalase and decreased malondialdehyde levels when compared to Group I, II and III. On histopathological analysis, the severity and extent of inflammation was less in 500mg/kg dose of leaf extract (Group V) than 250mg/kg of leaf extract (Group IV) and 100mg/kg of sulfasalazine (Group III). Tissue sections of Group V showed only few inflammatory infiltrates with absence of oedema and crypt abscess in the submucosal area. On examining the pathogenic versus beneficial bacterial load in the control and Group VI (PE 3) and Group VII (PE 4), papaya leaf extracts depicted antibacterial property and probiotic activity. In the present study, 500mg/kg of papaya leaf extract was efficacious in relieving oxidative stress and reducing inflammation in acetic acid induced ulcerative colitis in rats. Carica papaya leaf extracts have a potential role to modify gut microbe with respect to its prebiotic activity.