Objective To explore a rat model for disease pathogenesis and drug discovery research of microvascular dysfunction by comparing two modeling method : sodium laurate injury of endothelium and microsphere embolization. Methods Thirty male SD rats were randomly divided into sham operation, sodium laurate, and microsphere embolization groups with 10 rats in each group. After anesthetizing the rats, their chest was opened. Then, 0. 2 mL sodium laurate (1 g / L) or embolization microspheres ( 40 ~ 120 μm, 1 × 103 ) were injected into the left ventricle. The sham operation group was injected with an equal volume of normal saline. Rats were anesthetized to determine relevant indicators and then sacrificed to obtain materials at 24 hours after surgery. Results In the sodium laurate group, coronary microvessel thrombosis and myocardial cell injury were observed, but there were no differences in cardiac functions, hemodynamics, or myocardial enzyme indexes compared with sham operation. However, in the microsphere embolization group, coronary microvessel embolization and myocardial injury were observed. Moreover, left ventricular ejection fraction, left ventricular shortening rate, and the maximum rate of left ventricular pressure were decreased significantly and the activities of creatine kinase MB isoenzyme and lactate dehydrogenase were increased significantly. Conclusions Both modeling method induced coronary microcirculation dysfunction and damaged cardiac functions. The animal model established by microsphere embolization was more reliable than the other method. This method might be widely used to study pathogenesis and drug treatment of coronary microcirculation dysfunction.