Male Sprague-Dawley rats were treated ip for 30 d with either 3.0 mg Mn/kg or an equal volume of 0.9% NaCl, then sacrificed by exsanguination through the aorta under pentobarbital anesthesia. The pancreas was removed immediately, fixed in 10% buffered formalin, and subsequently processed for light microscopy. Significant pathological changes were observed in pancreatic tissue from Mn-exposed rats. These changes were characterized by a pancreatitis-like reaction consisting of expanded interacinar spaces, a thickened connective tissue capsule with invaginations of fibrotic connective tissue septa extending into the body of the gland, the presence of an inflammatory infiltrate of neutrophils, lymphocytes, and macrophages, and the separation of groups of acini from the body of the pancreas with occasional destruction of acinar cells. Since other peritoneal organs did not exhibit pathological changes, this study suggests that intraperitoneally injected Mn2+ exerts a selective toxicity on pancreatic tissue and that, therefore, intraperitoneal injection is not recommended as the route of administration of choice for chronic Mn neurotoxicity studies.