Chemical insecticides are still the main part of vector mosquitoes control program. The effectiveness is eventually reduces as mosquitoes become resistant to them with repeated use. Therefore, understanding the mechanisms of resistance will be required. The present study was carried out to evaluate the potential biochemical mechanism in contributing toward insecticide resistance in Culex pipiens field populations in Egypt. Natural populations of Culex pipiens were collected from Giza, Beheira, Sohag and Monufia Governorates. The present finding showed difference in enzyme activity in Culex pipiens natural populations compared with laboratory colony. Monufia populations show the highest level of beta and alpha esterases (9.2 and 5.7 times higher activity than S-lab respectively). The most significant values of GST were in Sohag and Giza populations (3.8 and 2.4 times higher activity than S-lab respectively). A significant increase in specific carboxylesterases was detected only in Beheira populations (1.8 times higher activity than S-lab). Mechanisms of resistance are discussed in relation to biochemical assay results.