In insects, biochemical mechanisms of insecticide resistance base on increasing of activities of main detoxyfying enzymes – monooxygenases, nonspesific esterases, and glutathion-S-transferases. Currently, the progress of resistance development and the degree of contributing enzymes to resistance in insects have been studied for certain insecticides. The goal of this study was to assess activities of monooxygenase, carboxylesterase, glutathione-S-transferase, and alkaline phosphatase in females and males housefly Musca domestica in the second, fourth, sixth, eighth and tenth generations of the chlorfenapyr-selected strain. Evaluation of chlorfenapyr susceptibility showed that adults M. domestica in tenth generations was tolerating to chlorfenapyr as the resistance ration value was 3.6. In certain generations of chlorfenapyr-selected strain M. domestica, monooxygenase activities in males and females were 1.4-2.1 times more, and alkaline phosphatase activities in females were 2.3-2.7 times more than that in control insects. Glutathione-S-transferase activities had no significant differences in adults M. domestica of control and chlorfenapyr-selected strains. For chlorfenapyr-selected strain M. domestica, activities of monooxygenase, carboxylesterase, and alkaline phosphatase differed in males and females of same generations that suggests that mode and pattern of resistance development might be sex-specific in this specie.