Objective To explore an effective method for establishing a dual-target mouse model of angiogenesis in myocardial ischemic and atherosclerotic plaque. Methods Ten C57BL/6 J mice were fed basic forage as a control group, while ten ApoE^{-/ -} mice were fed high-fat forage as a model group. After 8 weeks, the model group was subcutaneously injected with isoproterenol at 100 mg/ kg once a day for 2 days, while the control group was subcutaneously injected with the same amount of physiological saline. Another 4 weeks later, the serum levels of TC, TG, LDL-C, and HDL-C were measured. HE staining was used to estimate the pathomorphological changes in aortic tissues and different regions of myocardium. Immunohistochemical staining was used to measure the density of new vessels in aortic plaques and different regions of the myocardium that were marked by CD31. Results The levels of serum TC and LDL-C in the model group were significantly higher than those in the control group ( P < 0. 05), while HDL-C was significantly lower than that in the control group ( P < 0. 05). HE staining revealed pathological changes typical of AS in the aorta of the model group.After 4 weeks of the subcutaneous injection of isoproterenol, pathological changes typical of myocardial infarction were observed in HE staining of myocardial tissue in the model group. CD31 immunohistochemical staining showed that the density of new vessels in aorta of the model group was significantly higher than that in the control group ( P < 0. 05). The expression of neovascularization in the myocardial ischemia zone was the highest in the model group, which was significantly higher than that in the myocardial infarction zone and normal myocardium zone ( P < 0. 05). Conclusions ApoE^{-/ -} mice with myocardial infarction induced by subcutaneous injection of isoproterenol under a diet of high-fat forage can be successfully used to establish a dual-target mouse model of angiogenesis in myocardial ischemia and atherosclerotic plaque.