A series of trifluoromethyl pyridine derivatives containing 1,3,4-oxadiazole moiety was designed, synthesized and bio-assayed for their insecticidal activity. The result of bio-assays indicated the synthesized compounds exhibited good insecticidal activity against Mythimna separata and Plutella xylostella, most of the title compounds show 100% insecticidal activity at 500 mg L⁻¹ and >80% activity at 250 mg L⁻¹ against the two pests. Compounds E18 and E27 showed LC₅₀ values of 38.5 and 30.8 mg L⁻¹ against Mythimna separata, respectively, which were close to that of avermectin (29.6 mg L⁻¹); compounds E5, E6, E9, E10, E15, E25, E26, and E27 showed 100% activity at 250 mg L⁻¹, which were better than chlorpyrifos (87%). CoMFA and CoMSIA models with good predictability were proposed, which revealed the electron-withdrawing groups with an appropriate bulk at 2- and 4-positions of benzene ring could enhance insecticidal activity.