The aim of the study was to investigate the protective and therapeutic effects of Polygonum cognatum Meissn (PC) in the treatment of colitis. Rats were orogastrically treated with PC (2g/kg) throughout a 10-day interval before and/or after colitis, which was induced by intracolonic administration of acetic acid. Microscopic damage scores and scanning electron microscopy changes of colon segments were analyzed. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) in serum, malonyldialdehyde (MDA), glutathione (GSH), tissue factor (TF) levels, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and gammaglutamyltransferase (GGT) activities in the colon tissues were measured. PC treatment ameliorated the acetic acid-induced disturbances in colonic tissue. Serum IL-6 and TNF-a levels decreased with PC treated colitis group. Colonic tissue GGT, MPO activities and MDA levels were decreased on the other hand SOD, CAT activities and GSH levels were increased in PC treated colitis group. PC was effective in the treatment of acetic acid-induced colitis in rats. This may be due to the supression and down regulation of mediators in intestinal inflammatory response and the expression of antioxidant and anti-inflammatory response. In conclusion, PC can play an protective role by downregulating the colonic tissue damage and oxidative stress which may be related to modulating the activities of antioxidant molecules in rat model of colitis.