Abstract: Objective To investigate the effects of external counterpulsation (ECP) on shear stress and signal transduction in canines with myocardial infarction. Methods Nineteen healthy dogs were randomly divided into control, ischemia, and ischemia plus ECP groups. Myocardial infarction was induced in the latter two groups by ligation of the left anterior descending artery (LAD). Serum and aorta NO levels of the dogs were determined by modified nitrate reductase method, and serum and aorta cyclic guanosine monophosphate (cGMP) levels by radioimmunoassay. Results The shear stress in the truncus brachiocephalicus decreased after LAD ligation, but increased significantly after 2 h of ECP treatment. Serum and aorta NO levels in ECP and control groups were significantly higher than those in the ischemic group (P<0.05). Serum and aorta cGMP levels in control group and ECP group after LAD ligation were also significantly higher than those in the ischemic group (P<0.05). Conclusion ECP can increase the shear stress and increase NO and cGMP levels in dogs with myocardial ischemia, which might be an important mechanism of ECP for protection of the ischemic myocardium.