The invention discloses a placental growth factor loaded nano-particle, as well as a preparation method and application thereof. The method comprises the following steps: 1, dispersing an internal water phase (a water solution containing placental growth factors) in an oil phase (an organic solution containing poly(lactic-co-glycolic acid) and an organic solvent) to form colostrum, wherein the polarity of the organic solvent is 4.0-6.0, and the ratio of the internal water phase to the oil phase is (1:3)-(1:10); 2, emulsifying the colostrum in an external water phase (a water solution containing a hydrophilic nonionic surfactant with HLB of 8-18) to form multiple emulsion, wherein the ratio of the oil phase and the external water phase is (1:3)-(1:6); 3, mixing the multiple emulsion and an expanded phase (water or a water solution containing a stabilizing agent), removing the organic solvent and the stabilizing agent, and lyophilizing, wherein the ratio of the external water phase to the expanded phase is (1:5)-(1:15). The placental growth factor loaded nano-particle has a good sustained-release effect, the preparation method can be used for reducing protein degeneration and improving encapsulation efficiency and has a good stability, the organic solvent cannot be dichloromethane or other solvents, and the reaction toxicity can be reduced.