Insecticide resistance is a major obstacle to the management of diseasevectoring mosquitoes worldwide.The genetic changes and detoxification genes involved in insecticide resistance have been extensively studied in populations of insecticide-resistant mosquitoes,however few studies have focused on the resistance genes upregulated upon insecticide exposure and the possible regulation pathways involved in insecticide resistance.To characterize the changes in gene expression during insecticide exposure,and to investigate the possible connection of known regulation pathways with insecticide resistance,we conducted RNA-Seq analysis of a highly permethrin-resistant strain of Culex quinquefasciatus following permethrin exposure.Gene expression profiles revealed a total of 224 upregulated and 146 downregulated genes when compared to a blank acetone carrier treated control,respectively,suggesting that there were multiple,but specific genes involved in permethrin resistance.Functional enrichment analysis showed that the upregulated genes contained multiple detoxification genes including a glutathione S-transferase and multiple cytochrome P450 genes,as well as several immune-related genes,while the downregulated genes consisted primarily of proteases and carbohydrate metabolism and transport.Further analysis showed that permethrin exposure resulted in a decrease in the expression of serum storage proteins and likely represented a delay in the development of the fourth instar possibly due to a decrease in feeding.This effect was more pronounced in an insecticide-resistant strain than in an insecticide-susceptible strain and may represent a behavioral mechanism of insecticide resistance in Culex mosquitoes.