Objectives: Enhanced External Counterpulsation (EECP) is an effective non-invasive treatment of coronary artery disease. Its mechanism of action remains unknown. An acute coronary occlusion dog model was created to explore the angiogenesis effect of EECP. Methods: 12 Beagle dogs were anesthetized with 3% sodium pentobarbital, 1 mg/kg intraperitoneal injection and mechanically ventilated for the development of myocardial infarction. After coronary occlusion, the 12 dogs were randomly assigned to either EECP (N = 6) or control (N = 6). Immunohistochemical studies of actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local Vascular Endothelial Growth Factor (VEGF) were identified by ELISA and Reverse-transcriptional PCR analysis. Results: There was a significant increase in the density of microvessels per mm2 in the infarcted regions of EECP group compared to control group (vWF, 15.2±6.3 versus 4.9±2.1, p<0.05; actin, 11.8±5.3 versus 3.4±1.2, p<0.05). The positive stained area per mm2 also increased significantly ( actin, 6,600±2,900 versus 600±500, p<0.05; vWF, 5,700±1,900 versus 1,700±1,400, p<0.05). Immunohistochemical staining and RT-PCR analysis documented a significant increase in VEGF expression. These factors associated with angiogenesis corresponded to improved myocardial perfusion by ^99mTc-MIBI SPECT. Conclusion: Angiogenesis may be a mechanism of action for the improved myocardial perfusion demonstrated after EECP therapy.