Abstract: A synthesis method for selamectin was developed, where doramectin is oxidized by manganese dioxide, oximated and de-sugared in one-step by an aqueous solution of hydroxylamine hydrochloride, and then selectively reduced in the presence of Wilkinson's catalyst and hydrogen to obtain selamectin. Doramectin is oxidized to a carbonyl group firstly, so that the generation of impurities during the subsequent reaction is reduced; t-butyl alcohol with a larger steric hindrance is used as a solvent, so that transesterification impurities are avoided; the hydrogenation is implemented in the final step, and the crude product is recrystallized before the hydrogenation reaction, so that the cost is greatly reduced. The method of the present application with an overall yield of 57%. The purity of product was 97.11%. All impurities meet the requirements of Pharmacopoeia. The present application is a simpler, more economical and more efficient synthesis method, and is suitable for industrial production.