Objective To investigate the effects of magnetic alprostadil lipid microsphere in targeted treatment of ischemia-reperfusion injury in abdominal flaps of rats. Methods An animal model of ischemia-reperfusion injury in abdominal flaps of rats was developed. The study group was injected with magnetic alprostadil lipid microsphere via the opposite femoral artery, while the control group injected with physiological saline, and the blank group was treated with no vessel blockage or medication after skin flap preparation. At different time points of ischemia and reperfusion of the skin flaps, the blood flow volume and the content of MDA and NO in the flap tissues were determined by a laser Doppler Flowmetry, thiobarbituric acid method, and nitrate reductase method, respectively. At 7d after suture in situ of the skin flaps, the designed area and survived area of the skin flaps were determined by coordinate decal method, based on which, the survival rate of the skin flaps was calculated. Meanwhile, routine histopathologic slides of the flap tissues were taken for immunohistochemical staining to identify the expression of vascular endothelial growth factor (VEGF). Results The study group had significantly higher micro-circulation volume, NO synthesis quantity, VEGF expression density, and 7-d survival rate and significantly lower MDS level of the skin flaps than the control group and blank group. Conclusion As a high-performance bioactive compound, alprostadil can improve the micro-circulation and lighten the ischemia-reperfusion injury by increasing NO content and protecting the vascular endothelium of skin flaps.