Abstract:Objective This study aimed to establish a glycolipid metabolic disorder model in Zucker Diabetic Fatty (ZDF) rats induced by Purina 5008 feed and systematically evaluate its pathological characteristics to provide a preclinical model tool for mechanistic research and drug development. Methods Twelve-week-old male ZDF rats were selected as the model group (n=9), and Zucker Lean (ZL) rats served as the normal control group (n=9). The model group was fed Purina 5008 feed, while the control group received standard feed for 7 weeks. Observations included physical sign scores, body weight, Lee’s index, food and water intake, fasting blood glucose, oral glucose tolerance, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR). Pathological changes in the liver, pancreas, and aorta were analyzed via hematoxylin eosin (H E) and Oil Red O staining. Results Compared to the control group, the model group exhibited significant increases in physical sign scores (P<0.01), including polydipsia, polyphagia, dull fur, and soft feces. Body weight, Lee’s index, food/water intake, fasting blood glucose, serum TC, TG, LDL-C, ALT, AST, and HOMA-IR were markedly elevated (P<0.01). Pathological examination revealed severe hepatic steatosis, vacuolar degeneration of pancreatic islet cells, and disorganized aortic wall structure with uneven thickening in the model group. Conclusion The ZDF rat model induced by Purina 5008 feed stably simulates core pathological features of glycolipid metabolic disorders, including metabolic dysregulation, insulin resistance, and multi-organ damage, offering a reliable platform for mechanistic studies and therapeutic evaluation.