We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases.