The invention belongs to the field of pharmaceutical preparations, and relates to a long-acting sustained release preparation for preventing or treating retinal damage, and a preparation method thereof. The long-acting sustained release preparation takes erythropoietin (EPO) as an active component, takes dextran as a protective agent for the active component, and takes poly(lactic-co-glycolic acid), polylactic acid or polycaprolactone as a coating component to prepare sustained release microspheres, wherein the erythropoietin is coated by the poly(lactic-co-glycolic acid), polylactic acid or polycaprolactone. Proven by animal experiments, the sustained release microspheres of the long-acting sustained release preparation provided by the invention have the same protective actions on the ganglionic cells of damaged retinas by single vitreous chamber injection and repeated EPO protein vitreous chamber injection, and the sustained release microspheres are capable of avoiding a series of complications caused by many times of injection and overcoming the defects of repeated intraocular injection administration and gene therapy. The long-acting sustained release preparation provided by the invention adopts intraocular local administration, can reduce the dosage and treatment cost, and can not generate adverse effects on other organs or tissues in vivo.