In this study, potential protective and curative effect of probiotics on acetic acid-induced ulcerative colitis were evaluated. Ulcerative colitis was induced in rats by 2 ml of 3% glacial acetic acid (v/v) administered intracolonially for 3 successive days. Forty male albino rats were divided into Five equal groups. Group I: (Control group) rats received no drugs. Group II: Early UC-induced group, Group III: Late UC-induced group, Group IV: (Early UC + probiotics protected) rats received probiotics (135 mg/kg b. wt/day) orally for 21 days prior to acetic acid administration then sacrificed. Group V: (Late UC + probiotics treated) rats first administered with acetic acid then after 3 days probiotics was received for 21 days. A significant increase in L-MDA and Myeloperoxidase (MOP) and up-regulation of IL-1β, caspase-3 with down-regulation in Bcl-2 gene expression as well as marked decrease in GSH and CAT were observed in colon tissue of UC-induced rats. However, administration of probiotics to UC-induced rats caused a marked improvement and reverse all previous parameters near the average range. On conclusion, Probiotics protect colonic mucosa against ulcerative colitis and may be effective in enhances the healing of ulcerated colon via anti-inflammatory and anti-apoptotic activities and regenerating endogenous antioxidant mechanism.