Ulcerative colitis(UC) is a common chronic inflammatory bowel disease characterized by the upregulation of oxidative stress and pro-inflammatory cytokines. Probiotic bacteria and Ursodeoxycholic acid(UDCA) have been suggested as promising choices for the treatment of UC. The purpose of the current study was to assess the impact of probiotics and/or UDCA on acetic acid-induced colitis in rats. Methods: Rats were randomly categorized into seven groups:normal control, UDCA, probiotic, acute colitis, acute colitis+probiotic, acute colitis+UDCA, and acute colitis+Probiotic+UDCA. UDCA(10mg/kg/day)or Probiotic(0.5 mg/kg/day) was orally administered for 7days after24hours of induction of ulcerative colitis by 4%acetic acid. The rats were euthanized 24h after the last dose of treatment and on the 8thday post acetic acid instillation. Clear serum was separated for estimating immunological parameters as well as colon sections were evaluated for macroscopical, histopathological and oxidative stress. Results:Treatment with probiotics and or UDCA significantly reduced disease index, wet/dry colon weight ratio, ulcer area, and macroscopic disease scores, with some histopathological changes. Probiotics and/or UDCA also effectively reduced the levels of myeloperoxidase and malondialdehyde(90.6%,75.9%,84.6%) and increased glutathione levels(5.5%,39.4%,45.6%). Regarding the inflammatory markers, probiotics and/or UDCA reduced significantly pro-inflammatory cytokine levels such as interleukin-17 and 6, and C reactive protein, associated with increases in anti-inflammatory cytokine IL10. Conclusions: According to our findings, oral administration of probiotics and/or UDCA ameliorates acetic acid-induced colitis in rats via decreasing oxidative stress and modulating the pro-inflammatory cytokine levels and MPO activity. Therefore, these treatments may be an effective therapeutic candidate for ulcerative colitis treatment.