Objective  To investigate the effect of nobiletin on plateletactivating factor (PAF) metabolism in diabetic rats with renal injury.  Methods   Totally 72 rats were randomly divided into control group (n=10) and modeling group (n=62). The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group, aspirin group (20mg/kg), and nobiletin low(50mg/kg), medium(100mg/kg), and high-dose (200mg/kg) groups, each with 10 rats. After continuous oral administration for 6 weeks, rat body weight, kidney weight, and kidney index were measured. Histopathological assessments were conducted by using HE, periodic acid-Schiff staining (PAS), Masson staining, and transmission electron microscopy. Blood glucose levels, renal function, inflammatory factors, PAF and its regulatory factors were detected. Expression levels of PAF metabolism-related proteins, PAF-acetylhydrolase(PAFAH), PAF receptor (PAFR), and cholinephosphotransferase 1(CHPT1) in kidney tissues were assessed using Western blotting and immunohistochemistry.  Results   Following nobiletin intervention, rat body weight increased while kidney weight and kidney index decreased. Improvement in renal tissue pathology was observed, with reduced interstitial fibrosis and thinner basement membrane. Fasting blood glucose and glycated hemoglobin decreased, while fasting insulin showed no significant improvement. Urea nitrogen, blood creatinine, cystatin C, and 24-hour urinary protein excretion were reduced. Levels of interleukin (IL)-1α, IL-6, IL-8, and tumor necrosis factor (TNF-α) were lowered. PAF and its regulatory factors decreased. PAFR and CHPT1 expression decreased, while PAFAH increased.  Conclusion   Nobiletin can alleviate renal injury in diabetic rats with renal injury, improve kidney function, regulate blood glucose, and mitigate inflammatory response. Its mechanism may be associated with the modulation of platelet-activating factor metabolism.