Background: The role of neutrophils in experimental colonic damage induced by dextran sulfate sodium is uncertain. We test the hypothesis that neutrophils are of pathogenic significance and anti-neutrophil serum will attenuate the colonic damage induced by oral dextran sulfate sodium in rats. Methods: Rabbit anti-rat neutrophil Serum (anti-neutrophil serum) or control rabbit serum was administered to, and circulating neutrophil count was monitored in, rats before and during feeding of dextran sulfate sodium or regular rat diet for 2 weeks. Histologic features of mucosal damage were evaluated in hematoxylin and eosin-stained proximal and distal colonic sections by a blinded observer. Results: Oral dextran sulfate sodium induces weight loss, diarrhea, peripheral neutrophilia, and colonic damage. Anti-neutrophil serum induced neutropenia and significantly attenuated the weight loss, the neutrophil infiltration in the colon, and the mucosal necrosis and pathologic index in the distal colon. Conclusion: The data showing that anti-neutrophil serum attenuates distal colonic mucosal injury induced by dextran sulfate sodium support the hypothesis that neutrophils play a pathogenic role in this model of colonic mucosal damage.