Abstract: AIM To investigate the role of activation of the SHH signaling pathway in promoting vasculogenesis in rats with acute myocardial infarction and investigations of these mechanisms. METHODS Sixty male Sprague-Dawley rats weighing approximately (150-200) g were subjected to left anterior descending coronary artery ligation. The rats were randomly divided into three groups: acute myocardial infarction (AMI) operation group, exogenous recombinant human SHH protein group (rhSHH treatment group) and a cyclopamine treatment group. Collateral microvessel density was measured by VIII factor immunohistochemical analysis, and VEGF, bFGF and Ang-1 expressions in ischemic myocardium of acute myocardial infarction rats were observed using ELISA and RT-PCR. Effects of SHH expression on pathway signal protein expression were analyzed using Western blot method. RESULTS Compared with those in AMI group, treatment with rhSHH following AMI increased microvessel density (P<0.05), reduced myocardial infarction area (P<0.01), enhanced coronary collaterals by stimulating plasma level and mRNA expressions of VEGF, bFGF and Ang-1 in ischemic myocardium (P<0.01), and increased the relative density of protein levels of SHH, SMO and Gli-1 (P<0.05). However, these effects were significantly suppressed by the application of the inhibitor of cyclopamine (P<0.01). CONCLUSION Activation of SHH signaling pathway in rats with acute myocardial infarction increases the expressions of VEGF, bFGF and Ang-1, which promotes angiogenesis in rats with acute myocardial infarction.