The invention provides a preparation method of an azithromycin freeze-drying agent for injection. The method comprises the following steps of S1, mixing and dissolving raw materials: adding a cosolvent into water for injection, adding a pH regulator to regulate the pH value to 5.0-5.2, adding azithromycin into the water for injection, and performing stirring until the azithromycin is dissolved toform a mixed liquid medicine A; S2, performing decolorizing and impurity removing: regulating the pH value to 6.0-7.0 by adopting the pH regulator, adding activated carbon for needles, performing stirring for 15-20 min at the room temperature, and performing sterilizing, filtering and decarbonizing to form a mixed liquid medicine B; and S3, performing freeze-drying: a, repeatedly performing pre-freezing, b, performing primary sublimation drying, and c, performing drying again, wherein the cosolvent is citric acid, sodium hydroxide, mannitol and cis-6-nonen-1-ol, and the raw materials include the following components in parts by weight: 100 parts of the azithromycin, 50-60 parts of the citric acid, 20-30 parts of the sodium hydroxide, 30-40 parts of the mannitol, 3-5 parts of the cis-6-nonen-1-ol and 1500-2000 parts of the water for injection. The preparation method of the azithromycin freeze-drying agent for injection is good in solubility and high in stability, and the clarity of a prepared injection solution is high.