Background Enhanced external counterpulsation (EECP) has been demonstrated to be effective in the treatment of patients with coronary artery disease (CAD). It has been proposed that the beneficial effects of EECP observed in clinical studies may be due to the formation of new blood vessels (angiogenesis) and collateral development. However, there is a relative paucity of basic studies to support the proposed mechanisms. Methods Twelve 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, all animals were randomly assigned to either EECP or control. EECP was given one hour per day, 5 days a week, for a total of 28 to 30 hours treatment over a 6-week course. Immunohistochemical studies of α-actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local vascular endothelial growth factor (VEGF) were identified by enzyme linked immunosorbent assay (ELISA) and reverse-transcriptional polymerase chain reaction (RT-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