Toxic chemicals ingested as the result of environmental exposures or other risk factors such as cigarette smoking may increase the risk of developing cancer and other diseases such as diabetes. 2-Aminoanthracene (2-AA) was investigated to determine toxic effects of chronic dietary exposure upon major organ systems including the pancreas. Fisher-344 rats were fed 2-AA (50-100 mg/kg of diet) and euthanized at 14, 30, 63, and 80 days. Growth, tissue histological, immunocytochemical, and clinical pathological end points were examined at each time point. Significantly elevated plasma glucose and glycated hemoglobins and reduced serum protein levels were recognized after 80 days of feeding (100 mg/kg of diet 2-AA group). Similar results were observed in rats exposed to 75 mg/kg of diet but appeared to be absent in the 50-mg/kg group. An unexpected pattern of responses suggestive of diabetic sequelae was observed in a glucose tolerance test conducted during the seventh week. After 63 and 80 days, large cytoplasmic vacuoles in islet cells were observed by light microscopy. In addition, the immunocytochemical study demonstrated beta cell insulin insufficiency at 63 and 80 days. No inflammatory infiltration of the islets was observed. These findings suggest that depletion of secretory granules occurred in the beta cells. Necrotic changes occurred in the acinar cells of the pancreas with increasing duration and dose of 2-AA. The cytological, immunocytochemical, and histological results demonstrate that chronic dietary exposure to 2-amino anthracene alters the endocrine and exocrine pancreas cellular morphology and induces diabetic-like symptoms in the Fisher-344 rat.