Pyrethroids are the most commonly used insecticides in the vector control programs. This insecticide group is one of the common recommended groups by the World Health Organization (WHO) for mosquito control. Recently, Pyrethroid resistance had rapidly spread worldwide which had its consequences on the effectiveness of control programs and threats public health. In this study, selection of Pyrethroid resistance in field-collected population of Culex pipiens was monitored after exposed to 0.05% Lambda-cyhalothrin for multiple generations. Activities of three detoxification enzymes namely; Oxidases, Nonspecific Esterases and Glutathione-S-transferases (GST), that synchronized with the resistance development, were monitored. Enzyme activities showed proportional relationship to Pyrethroid resistance. The results presented in this study will elucidate the Pyrethroid resistance development and its relation to the metabolic mechanisms. This may explain the complexity of resistance mechanisms in vector management and help to mitigate control failure due to insecticide resistance.