Objective The purpose of the present study was to develop an animal model of type Ⅱ diabetic coronary heart disease in Zuker diabetic fatty (ZDF) rats. Methods The ZDF rat model of type Ⅱ diabetic coronary heart disease was prepared by high-fat diet feeding combined with continuous injection of isoprenaline hydrochloride (ISO) in a dose of 1 mg·mL^-1 for 10 consecutive days. Serum creatine kinase (CK), and creatine kinase izozyme (CK-MB), ST segment in electrocardiogram (ECG) and myocardial pathological changes were detected to evaluate the rat model. Results CK of both the control and model groups was gradually increased with ISO injections, while CK-MB increased first and then decreased. The ST segment in ECG part Ⅱ had significant changes. The pathological examination found that about half of the myocardial cross section in the model group was necrotic after injections of ISO for 5 days and more than 3/4 of the myocardial cross section was necrotic after injection of ISO for 10 days. The results indicated that ISO caused myocardial injury in ZDF rats. Conclusions The variation of CK-MB, CK, ST segments in ECG and myocardial necrosis indicate that the model is successfully established. The use of high-fat diet combined with continuous injection of isoprenaline hydrochloride in a dose of 1 mg·mL is a simple way to develop a Zuker diabetic fatty rat model of type Ⅱ diabetic coronary heart disease.