The invention relates to a long-acting cefquinome sulfate injection and a preparation method thereof. The injection solution comprises, by weight, 2 to 3 parts of cefquinome sulfate, 2 to 3 parts of a suspending aid, 0. 5 to 1 part of a stabilizer, 0.2 to 0.4 parts of an antioxidant, 0.2 to 0.4 parts of a polylactic acid-glycolic acid copolymer, 0.3 to 0.7 parts of a crosslinking agent, 1 to 1.5 parts of a pH stabilizer and 80 to 120 parts of a dispersion medium. In preparation, the suspending aid, stabilizer, antioxidant, polylactic acid-glycolic acid copolymer, crosslinking agent and pH stabilizer are added into the dispersion medium, the mixture is cooled, then cefquinome sulfate is added into the cooled mixture and the mixture is ground. Compared with the prior art, the preparation method improves injection stability and dispersibility and prolongs pharmacodynamic metabolism time. The injection can be slowly released after intramuscular injection, realize a stable drug concentration in the blood, realize the effects the same to those of the multiple interval injection processes of the same type of the conventional dosage form only through one injection process, reduce drug use frequency, reduce a drug use cost and a labor cost and prevent stress response and can be easily stored.