Objective: A diabetic coronary atherosclerosis model was established by giving Bama minipigs high-fat diet, low dose streptozotocin combined with balloon injury. Methods: Eighteen healthy male Bama minipigs, aged 4 months old, were randomly divided into a control group (n=3) and a model group (n=15). The pigs in the control group were given normal diet. In the model group, pigs were fed with high-fat diet and intravenously injected with streptozotocin (100 mg/kg) followed by continuous glucose monitoring for 2 weeks, and a balloon injury was performed in the middle segment of right coronary artery at 3 weeks. Three pigs in the model group were randomly euthanized at 20 weeks, and the injured right coronary artery, uninjured circumflex coronary artery, carotid artery, renal artery, and pancreas were taken for histopathological examination. Results: Twelve pigs in the model group reached the diabetic standard and survived to the 20th week. Compared with the control group, body weight of the model group significantly decreased, and the levels of blood glucose, total cholesterol, low-density lipoprotein cholesterol, and triglyceride significantly increased (P<0.05). Significant intimal proliferation of the right coronary artery was shown in the balloon-injured vessels compared with the uninjured vessels in the model group and the right coronary artery in the control group (P<0.05). The number of islets and islet cells in the model group significantly decreased compared with those in the control group (P<0.05). At 36 weeks, the other 9 pigs in the model group were still in good condition. Conclusion: Low dose streptozotocin combined with balloon injury can accelerate the diabetic coronary atherosclerosis in Bama minipig model with high success rate, good safety, and long-term effectiveness.