This study evaluates the microscopic and immunohystochemical changes in the pancreas of 18 dogs with natural occurring diabetes mellitus (DM) and found extensive damage in 28% of them, and reduction of the number of well-granulated beta-cells in the remaining 72%, but no evidence of humoral autoimmunity directed towards pancreatic islets was not found. 8 of the dogs received intrahepatic islet allografts form multiple donors and treated with cyclosporine to prevent rejection. One dog failed to sustain euglycemia after 8 months, another died of pneumonia and the other 6 sustained euglycemia for 253 to 716 days.