Scientific advances in the 19th and 20th centuries led to the discovery of insulin, the fundamental therapeutic means for treatment of diabetes mellitus type 1 at the onset of the twenties, to the introduction of sulfonylurea derivatives and biguanides in the fifties and sixties. The discovery of the principle of radioimmunoassay at the end of the fifties made it possible to investigate insulin secretion and to achieve a more accurate understanding of the pathogenesis of type 1 and 2 diabetes. Understanding of insulin resistance made it possible to introduce an euglycaemic hyperinsulin clamp at the end of the seventies. Insulin resistance was presented in context with metabolic syndrome X. Insulin is administered at the break of the millenium in subcutaneous injections, insulin dispensers and insulin pumps, experimentally also by the intraperitoneal and inhalatory route. In the nineties in the practice of diabetes 1 therapy ultrashort-term and finally als long-term insulin analogues were developed. For type 2 diabetes mellitus inhibitors of alpha-amylase were introduced and as a quite new group of oral antidiabetics thiazolidindiones. The possibility of 24-hour monitoring of the blood sugar level by means of a subcutaneous glucose sensor was introduced. The end of the century is characterized also by attempts to administer growth factors in the treatment of non-patent vascular obstructions in the diabetic foot syndrome. In mice and rats transformation of the ductal cell of the exocrine pancreas to the Langerhans islet cell proved successful. Further progress in diabetology will depend, similarly as in the rest of medicine, in particular on advances in cellular and molecular biology and genetics, as well as advances in microelectronics and new materials. Emphasis on the community understanding of this disease and consequential primary prevention of diabetes and secondary prevention of its complications are important.