Resistance development against some frequently used insecticides, i.e., deltamethrin (1.5% EC), cypermethrin (10% SC), permethrin (0.5% WP) and DDVP (50% EC) was evaluated against Musca domestica L. Insecticide bioassays were carried out against susceptible and resistant strains at 2.5, 5, 10, 20 and 40 μg/μl concentrations. Mortality data was recorded after 24, 48 and 72 hours. Resistance was monitored up to three generations and the flies with higher LD₅₀ values than the F1 generation were considered resistant. LD₅₀ values for Permethrin increased from 58.258 μg/μl to 85.1375 μg/μl with highest resistance ratio (RR) in F1 to F3. The lowest resistance ratio was observed with DDVP. Maximum inhibition in adult emergence was observed against DDVP. The inhibitory activity of Esterases; Acetylcholine and Phosphatases; ACP, AKP was recorded. Deltamethrin inhibited the maximum activity of AChE (50%), whereas, DDVP caused maximum inhibition of acid phosphatases. The results suggested that house fly populations are more resistant to pyrethroids compared to organophosphate insecticides.