Pancreatic islet transplantation (IT) is a promising treatment for type 1 diabetes (T1D), offering the potential to restore endogenous insulin production and achieve long-term blood glucose control. However, challenges such as organ shortages, immune rejection, and the need for immunosuppression remain significant obstacles. Recent advances in IT have improved clinical outcomes, with studies showing that patients can achieve insulin independence and better glycemic control. The Edmonton protocol, introduced in 2000, has been pivotal in improving the long-term success of IT. Long-term follow-up studies indicate that IT can significantly reduce complications and improve quality of life for T1D patients. Stem cell-derived islet β-cells and porcine islets are emerging as potential solutions to the shortage of donor islets. Stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), can be differentiated into β-cells in vitro, offering a renewable source for islet transplantation. Porcine islets, which are more readily available and have insulin similar to human insulin, are also being explored for xenotransplantation. However, challenges such as immune rejection and the need for immunosuppression persist, and gene editing technologies like CRISPR/Cas9 are being investigated to improve the safety and efficacy of porcine islet transplantation. Islet encapsulation technology is another promising approach to reduce immune rejection by creating a protective barrier around islet cells. This technology allows islet cells to function while minimizing immune responses. Various biomaterials, such as alginate and polyethylene glycol diacrylate, are being used for encapsulation, with some showing promising results in preclinical studies. The optimal transplant site for islet cells is also under investigation. While the portal vein is the traditional site, it can lead to complications such as portal hypertension and immune rejection. Alternative sites, such as the omentum and subcutaneous space, are being explored for their potential to reduce immune rejection and improve islet survival. Combining islet transplantation with mesenchymal stem cells (MSCs) and regulatory T cells (Tregs) is another promising strategy to enhance immune tolerance and reduce the need for immunosuppression. These cells can modulate immune responses and promote islet survival. In conclusion, while IT has shown significant promise in treating T1D, ongoing research is needed to address challenges such as organ shortages, immune rejection, and the need for immunosuppression. Advances in stem cell technology, porcine islet transplantation, and encapsulation techniques are expected to further improve the safety and efficacy of IT, ultimately leading to better outcomes for patients with T1D.Pancreatic islet transplantation (IT) is a promising treatment for type 1 diabetes (T1D), offering the potential to restore endogenous insulin production and achieve long-term blood glucose control. However, challenges such as organ shortages, immune rejection, and the need for immunosuppression remain significant obstacles. Recent advances in IT have improved clinical outcomes, with studies showing that patients can achieve insulin independence and better glycemic control. The Edmonton protocol, introduced in 2000, has been pivotal in improving the long-term success of IT. Long-term follow-up studies indicate that IT can significantly reduce complications and improve quality of life for T1D patients. Stem cell-derived islet β-cells and porcine islets are emerging as potential solutions to the shortage of donor islets. Stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), can be differentiated into β-cells in vitro, offering a renewable source for islet transplantation. Porcine islets, which are more readily available and have insulin similar to human insulin, are also being explored for xenotransplantation. However, challenges such as immune rejection and the need for immunosuppression persist, and gene editing technologies like CRISPR/Cas9 are being investigated to improve the safety and efficacy of porcine islet transplantation. Islet encapsulation technology is another promising approach to reduce immune rejection by creating a protective barrier around islet cells. This technology allows islet cells to function while minimizing immune responses. Various biomaterials, such as alginate and polyethylene glycol diacrylate, are being used for encapsulation, with some showing promising results in preclinical studies. The optimal transplant site for islet cells is also under investigation. While the portal vein is the traditional site, it can lead to complications such as portal hypertension and immune rejection. Alternative sites, such as the omentum and subcutaneous space, are being explored for their potential to reduce immune rejection and improve islet survival. Combining islet transplantation with mesenchymal stem cells (MSCs) and regulatory T cells (Tregs) is another promising strategy to enhance immune tolerance and reduce the need for immunosuppression. These cells can modulate immune responses and promote islet survival. In conclusion, while IT has shown significant promise in treating T1D, ongoing research is needed to address challenges such as organ shortages, immune rejection, and the need for immunosuppression. Advances in stem cell technology, porcine islet transplantation, and encapsulation techniques are expected to further improve the safety and efficacy of IT, ultimately leading to better outcomes for patients with T1D.