The complications of diabetes continue to present significant health risks despite improvements in conventional insulin therapy. Transplantation of pancreatic islet tissue has the potential to provide more precise glucose regulation and possibly minimize these implications. Recent advances in pancreatic islet isolation technology have facilitated investigation of islet allograft function in large animal models. These studies are fundamental to the development of methods for transplantation of allogeneic or xenogeneic islets in diabetic patients. This paper reviews the approaches which have been taken to prevent rejection and allow assessment of islet allograft function in the pancreatectomized dog model. These approaches include immunosuppression, immunomodulation of the donor tissue and isolation of allogeneic tissue within an immunoprotective membrane.