Ulcerative colitis is characterized by oxidative / nitrosative stress and leukocyte infiltration which are shown to be important factors in the etiopathogenesis of colitis.The aim of this study was to evaluate the protective mechanism of the polysaccharide (PLS) fraction extracted from the seaweed Gelidium spinosum (PEGS) in Dextran Sulfate sodium; DSS-induced ulcerative colitis in male Swiss albino mice.The in vivo study was carried out with mice (pretreated with PEGS/mesalazine orally at 60 mg/75 Kg; 7 days; then 2.5 % (DSS); 7 days). Clinical symptoms (disease activity index; DAI), oxidative, nitrosative stress and inflammatory parameters were evaluated.The results revealed that PEGS lowered the symptoms of ulcerative colitis induced by DSS by reducing malondialdehyde, nitrosative and pro-inflammatory biomarkers (NO, S-nitrosothiol, peroxynitrite, TNF-α and IL-6). These significant protective effects of PEGS were associated with a remarkable decrease of the level of myeloperoxidase in a significant way.PEGS effectively increased the superoxide dismutase and catalase activities, and restored the glutathione metabolizing enzyme (glutathione peroxidase, glutathione S-transferase) in the colon tissue. In conclusion, these findings suggest that PEGS exerts beneficial effects in experimental colitis, and therefore we propose that it could be a potential drug in treating ulcerative colitis.