RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate a variety of methods to induce chronic pancreatitis and its radiologic expression by experimentally inducing this condition in cats. MATERIALS AND METHODS: Chronic inflammatory and fibrosing pancreatitis was produced in cats by intraductal injection of 1.5 mL of 94% ethanol in one group or by a combination of intraductal and intraparenchymal injection of ethanol together with partial obstruction of the main pancreatic duct to 70% of its original lumen by fixation of a small catheter in the papilla. For comparison, other cats underwent total obstruction of the main pancreatic duct. All groups, as well as untreated control cats (n = 3), underwent repeat laparotomy to obtain biopsy specimens. RESULTS: Cats with total obstruction showed progressing fibrosis with dilatation of ductules occasionally infiltrated with granulocytes. From 26 weeks on, acini and islets of Lnagerhans became atrophic. Radiographs showed progressive but diffuse dilatation of ducts, ductules, and side branches. Cats from the other two groups had interlobular inflammation and fibrosis with flattened and irregular ductular epithelium. Later, ductular proliferation occurred, interstitial inflammation subsided, and fibrosis increased. Radiographs showed very irregular ducts and ductules with stenosis and dilatation. From 26 weeks on, no substantial differences were observed between the cats who received only intraductal injection of ethanol and the cats who underwent the combination of procedures. CONCLUSION: The histopathologic and radiographic alterations that evolved from damage to the ductal epithelium in the cat resembled the features of chronic pancreatitis in humans and differed from those caused by total obstruction of the main pancreatic duct in cats.