In its prominent experimental studies salvianolic acid B (Sal B) is novel because of its well-defined, common physiological effects, which include anti-inflammatory, anti-depressant, cardioprotective, DNA protective, neuroprotective and hepatoprotective activity in experimental animals. Initially, Sal B was studied for its anti-inflammatory properties, used as a remedy for a wide range of disease conditions, but its specific efficacy on inflammatory bowel disease is still unclear. The aim of this current study was to understand the therapeutic potential of Sal B in an acetic acid (AA)—triggered experimental mouse colitis model. Colitis was triggered by intrarectal injection of 5% AA, and then laboratory animals were given Sal B (10, 20 and 40 μg/kg) for seven days. The ulcerated colonic mucosa was assessed by clinical experiment, macroscopical, biological and histopathological analysis. The results showed depleted SOD, CAT, GSH levels and consequential elevated MPO and MDA levels and aberrant crypt foci and mast cells were seen in the AA-induced colonic mucosa of experimental animals. The data obtained from this study demonstrate that a dose of 40 µg/kg showed an efficacious anti-ulcer effect against AA-induced experimental colitis. Based on its antioxidant efficacy, Sal B may therefore be useful as a therapeutic approach for ulcerative colitis.