The susceptibility of Culex pipiens larvae collected from Al-Asher of Ramadan, Sharkia Governorate, to chlorpyrifos and lambda-cyhalothrin insecticides was investigated for 20 successive generations. For multiple generations, the instar larvae of field parent strain were exposed to LC₃₀ of the previous generation to that insecticide. Total protein and lipids content as well as activities of detoxifying enzymes (i.e. acetylcholinesterase, non-specific esterases and glutathione-S-transferase) were determined in each generation. Bioassay tests showed that larval Cx. pipiens developed 144.31 and 761.85-fold resistance to chlorpyrifos and lambda-cyhalothrin, respectively, after 20 successive generations of selected pressure. Total protein content declined while total lipids increased gradually with proceeded the generations. In general, the activities of detoxifying enzymes increased gradually with raising generation numbers which indicate that the increased resistance is likely to be associated with the increased activity of target and metabolic enzyme systems.