Abstract: Kidney transplantation is an effective treatment for end-stage renal disease. However, post transplantation diabetes mellitus (PTDM) is a common complication after kidney transplantation, affecting 10% to 40% of recipients and increasing the risk of cardiovascular disease, infections, sepsis and other conditions. The pathogenesis of PTDM is complex, including pancreatic β-cell dysfunction and insulin resistance. Tacrolimus, a commonly used immunosuppressive drug, is an independent risk factor for PTDM. Its mechanisms include damaging pancreatic β-cells, mediating impaired mitochondrial autophagy, etc. In addition, tacrolimus also raises blood glucose levels through various pathways, such as affecting gut microbiota metabolism and activating bile acid signaling pathways. In recent years, some new anti-diabetic drugs have shown certain application prospects in kidney transplant recipients, but the evidence-based medical evidence for their combined use still needs further exploration. In the future, it is necessary to conduct in-depth research on the multiple sites of action of tacrolimus to reduce the occurrence of PTDM and improve the prognosis of kidney transplant recipients.