The invention discloses a selamectin ethosome preparation as well as a preparation method and an application thereof. The selamectin ethosome preparation is prepared from the following components: selamectin, egg yolk lecithin, alcohol (including ethanol and propylene glycol), tween-80 and a phosphate buffer solution. Compared with a selamectin transdermal agent, the selamectin ethosome preparation provided by the invention has the advantages of greatly reduced toxicity, good skin permeability, biological slow release, longer action time, good stability and high safety. The animal experimentsprove that the ethosome preparation disclosed by the invention has the effect of resisting infection of parasites in dogs and cats.