The early period established that immune compatibility and immunologic responses were central barriers shaping islet transplantation, prompting immunomodulatory strategies and histocompatibility research. The site and route of transplantation were actively tested, with portal vein, intraperitoneal, intra-splenic, and other contexts influencing engraftment in animal models. Advances in in vitro culture and preparation enabled viability maintenance and functional stability, enabling scalable islet isolation and preserving architecture for transplantation; evidence of disease-correcting potential emerged as grafts reversed hyperglycemia in diabetic models. Influential Works: The key milestones included demonstration that intact pancreatic islets can be transplanted and function in vivo, establishing feasibility and catalyzing subsequent work. A preliminary report of human islet transplantation initiated translational research by showing clinical feasibility. Methods for large-scale isolation and immunomodulatory strategies introduced in this period provided scalable preparation and extended graft survival, shaping subsequent advances.