A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of the left and right lobes of the pancreas facilitates the delivery of IORT, reduces the risk of pancreatitis and will demonstrate, eventually, minimal functional changes in the exocrine and endocrine pancreas at an earlier stage. Sixteen beagles were used. Investigations before and after the reduction procedure were intravenous glucose tolerance tests, serum insulin levels, faecal fat excretion, blood chemistry tests and body weight. Eight weeks after the pancreas reduction 15 dogs underwent an IORT procedure in which 25, 30 or 35 Gy IORT was delivered to the pancreatic remnant. We conclude that the pancreas reduction technique used to study the effects of IORT to the canine pancreas is feasible without mortality or morbidity. Endocrine and exocrine pancreatic function remained normal with a minimal follow-up of 3 months.