In an effort to discover new molecules with good insecticidal activities, more than 40 new avermectin derivatives were synthesized and their biological activities were determined against Tetranychus Cinnabarinus, Aphis craccivora and Bursaphelenchus xylophilus.Preliminary bioassays showed that most of the target compounds possessed good-to-excellent activities against three insect species.Notably, the majority of the target compounds exhibited high selectivity against T.cinnabarinus, some of which were much better in comparison with the commercial avermectin.Especially compounds 9j (LC50:0.005 μM) and 16d (LC50: 0.002aM) were 2.5-and 4.7-fold as high as the activity of avermectin (LC50:0.0131M), respectively, against T.cinnabarinus.Moreover, compounds 9b, 9d-f, 9h, 9j, 9I, 9n, 9p, 9r, 9v and 17d showed superior activities with LC50 values of 2.959-5.013 μM compared to that of 1 (LC50: 6.746 μM) against B.xylophilus.Meanwhile, the insecticidal activities of compounds 9f, 9g, 9h, and 9m against A.craccivora were 7~8 times better than that of avermectin, with LC50 values of 7.744, 5.634, 6.809, 7.939 and 52.234 μM, respectively.Furthermore, QSAR analysis showed that the molecular shape, size, connectivity degree and electronic distribution of avermectin analogues had substantial effects on insecticidal potency.These preliminary results provided useful insight in guiding further modifications of avermectin in the development of potential new insecticides.