For better management of the use of insecticide in public health against Culex quinquefasciatus, an arboviral and filarial vector, a study was conducted at Natitingou, a town located in northern Benin, from October 2015 to March 2016, to evaluate the susceptible of this mosquito to insecticides and the mechanisms of resistance developed. The protocol was based on mosquito collection during both dry and rainy seasons across the four areas selected in northern Benin. Bioassays were performed on adult mosquitoes collected from the field to assess the susceptibility of filarial vectors to insecticide-impregnated papers (permethrin 0.75%, delthamethrin 0.05%, DDT 4%, and bendiocarb 0.1%) following WHOPES guidelines. Moreover, mosquitoes from the susceptible tests were used to search for the presence of the knock down resistance (Kdr) and the Acethylcholinesterase (Ace-1R) mutations. Finally, F1 generation of the wild population of Cx. quinquefasciatus were used for biochemical analysis to target Mixed Function Oxidase (MFO), non-specific esterase (NSE) and glutathione-S-transferases (GST) enzymes. This research showed: 1)- A wide spread of resistance to permethrin, delthamethrin and DDT was found in samples of Cx. quinquefasciatus despite the collection areas with 4%; 7% ; 19% and 60% as average of mortality respectively with DDT, permethrin, deltamethrin and bendiocarb; 2)- The kdr mutation was detected in all areas at various frequencies (0.8 to 0.88) whereas the Ace-1 mutation was found at a very low frequency (≤ 5%); 3)- Enzymes activities (oxidase, esterase and glutathion-S-transferases) were detected in all mosquito populations despite the areas of collection. This work has highlighted the high resistance of Cx. quinquefascitus to the 3 classes of insecticides used in public health. Moreover, the high frequency of kdr and the presence of enzyme activity in Cx. quinquefasciatus will augment the existing data on the insecticide resistance of filariasis vectors and will be useful for making decision to control this mosquito.