A series of novel symmetrical and asymmetrical 2,5-disubstituted-1,3,4-oxadiazoles and their intermediates were synthesized. A convenient procedure for preparation of aromatic nitrile and ester intermediates is reported. The insecticidal activities of oxadiazoles against Dropsophila melanogaster were recorded, and analysis of structure-activity relationships showed that the highest occupied molecular orbital energy (E(H)) was the main factor to affect the bioactivities.