The invention discloses a preparation method and application of a pyridazinone myocardial perfusion PET radiopharmaceutical. According to the invention, a large-dose initial 18F activity label is adopted, the precursor usage amount of a reaction, the reaction temperature and the purification HPLC condition are optimized, the reaction yield is improved, the preparation amount of [18F]Fmpp2 can reach 200 mCi, the chemical impurity amount is reduced, the radiochemical purity is high, and the key quality index is kept stable within 6 hours. A method for preparing a [18F]Fmpp2 solution for injection is improved, and the radiochemical purity and stability of the [18F]Fmpp2 are improved. The [18F]Fmpp2 prepared by the invention is subjected to miniature pig myocardial model PET imaging display; after the [18F]Fmpp2 is intravenously injected, the myocardial radioactive uptake is high, and the influence of peripheral organs on myocardial development is small; and normal myocardium, ischemic myocardium caused by chronic coronary artery stenosis and infarcted myocardium caused by acute coronary artery stenosis can be distinguished.