Abstract: In order to find the high activity milbemycins derivatives. With ivermectin as the raw material, a series of 13-sulfonyl amidine-milbemycins derivatives (7a-7i) were synthesized after deglycosylation, hydroxy protection, oxidizing reaction, reductive amination and deprotection of C-13 of milbemycins. The preliminary bioassay showed that the compounds exhibited high insecticidal activity against Tetranychus cinnabarinus and Aphis craccivora. Some of them show a higher insecticidal activity, the LC50 value of 7g, 7h and 7i against T.cinnabarinus were 1.04×10-2, 9.60×10-4, 1.44×10-2 mg/L in 24 h, respectively, the LC50 value of 7i against A.craccivora were 7.80 mg/L. The results indicate that the structural modification of sulfonylation on the C-13 amine of milbemycins are helpful to improve the activity against spide mite and aphid.