RNase-L is protective against DSS-induced colitis and promotes recovery following GI injury. RNase-L−/− and WT mice were treated with 2.5% DSS w/v drinking water or regular water control for 9 days. Mice were euthanized at days 0, 1, 3, 5, 7 (n = 6) and 9 (n = 7). The clinical score (D) is representative of colitis severity and is comprised of: (A) % weight loss (B) stool score- a measure of stool consistency and (C) bleeding score- a measure of occult blood. (E) Colon tissue was measured and photographed before processing. RNase-L−/− and WT mice were treated with 2.5% DSS w/v drinking water for 7 days followed by 7 days of regular water (con = untreated) to examine recovery. Survival (F) is expressed as a percent of the surviving mice from the total number treated (n = 15 for days1-7, n = 10 post day 7) and untreated (n = 3). Significance was determined by Kaplan-Meier analysis. Data represent means ± SE. *p < 0.05, **p < 0.005.