Extracorporeal shock wave therapy (ESWT) can improve flap survival, but its mechanism remains unclear. In this study, we aim to investigate whether ESWT can improve blood flow in ischemic skin flaps and the possible mechanism. Cranially based random-pattern flap (3 × 10 cm) model was established, and its ischemic portion was treated with or without ESWT at 0.09 mJ/mm2 with 750 impulses (1.5 Hz), immediately after operation. Survival area, blood flow, vessel distribution, microvessel density, and expression of nitric oxide and vascular endothelial growth factor were evaluated at 1, 3, and 10 days postoperatively. The results showed that blood perfusion, expression of nitric oxide and vascular endothelial growth factor, vasodilatation of pre-existing vessels at early postoperative stage, neovascularization at late stage, and flap survival were all significantly promoted in treatment group. In conclusion, ESWT can improve skin flap surviving rate through enhanced vasodilatation at early postoperative stage and neovascularization at late stage via modulation of angio-active factors expression.