Objective To investigate the mechanisms of macrophage activity in the process of myocardial regeneration and explore the feasibility of eliminating macrophages after constructing a myocardial infarction model in CD11b^DTR newborn mice. Methods CD11b^DTR mice were injected with DT to eliminate macrophages on their day of birth after ligation of the left anterior descending branch of the coronary artery. This established a myocardial infarction model with macrophage elimination to explore the role of macrophages in the process of myocardial infarction. Results After ligating the left anterior descending branch of the coronary artery of CD11b^DTR mice on their day of birth to construct the myocardial infarction model, DT injection failed to significantly eliminate their macrophages. Macrophages could not be eliminated by increasing the administration frequency or concentration. Increasing the administration frequency and concentration at the same time had an obvious macrophage elimination effect, but the survival rate of the DT group mice decreased significantly, and the survival state of the surviving mice was very poor. Thus, this method cannot be used for subsequent experiments. Conclusions Mice injected with DT under physiological conditions showed significant macrophage elimination in the heart. However, after coronary artery ligation of CD11b^DTR mice to create a myocardial infarction model, macrophage elimination could not be obtained by injecting DT, which may be caused by the fact that coronary artery ligation prevented the DT from being delivered to the heart normally, preventing it from effectively acting on macrophages in this organ.