Ulcerative Colitis(UC) is one of the major inflammatory Bowel Syndrome(IBD) which show incremental incidence worldwide. In the present study, the potential protective and curative effects and the molecular mechanisms of Omega-3 polyunsaturated fatty acids(ω-3PUFAs) in rat model of acetic acid-induced UC were investigated. Forty male albino rats were divided into five equal groups. Group I:( Control normal group) received no drugs. GroupII:(Early ulcerative colitis-induced group)rats received 2 ml(3%v/v) glacial acetic-acid intra-colonially at the 21st day of the experiment and sacrificed 3 days later of acetic acid administration. Group III:(Early ulcerative colitis+omega-3protected group) rats received Omega-3(300mg/kg body-weight/day) orally for 21 days prior to glacial acetic acid administration and sacrificed 3 days later. Group IV:(Late ulcerative colitis-induced group) rats received glacial acetic-acid similar to group II for 3 successive days and sacrificed after 21 days. Group V:(Late ulcerative colitis+Omega-3 treated group) rats first administered with acetic-acid then after 3 days Omega-3 was administered for 21 days. The results showed significant increase in L-Malondialdehyde(L-MDA) and Myeloperoxidase(MOP) activity with marked decrease in reduced glutathione(GSH) and Catalase(CAT) activity in colon tissue of UC-induced rats as compared with control group. However, a significant depletion of colon tissue L-MDA,MOP activity and obvious increase in GSH concentration and CATactivity was observed after Omega-3 administration compared to UC-non-treated group. Additionally, a significant up-regulation of mRNA gene expression levels of (IL-1β), Caspase-3 and down-regulation in Bcl-2 observed in colon tissue of UC-induced rats. However,the expression levels of IL-1β and Caspase-3 were down-regulated and Bcl-2 was up-regulated after administration of Omega-3.