Piperonyl Butoxidc (PBO) is an insecticide synergist inhibiting the detoxification enzymes within insect tissues. PBO itself is not an insecticide, it is added to increase the potential effect of insecticides and it has an important role in reducing resistance levels and insecticide application rates. In this study, Drosophila melanogaster laboratory populations were exposed to the synthetic pyrethroids (Cypermethrin, Cyphenothrin, Deltamethrin and Permethrin) either alone or in combinations with different rates of piperonyl butoxide (PBO). Our results showed that the mixture of pyrethroids and PBO caused an increase in the mortality and knock down values and decreased knock down times more than pyrethroid alone, on D. melanogaster in a dose dependent manner up to a certain dosage. The results suggest that PBO ratios in insecticide formulations should be determined with efficiency tests according to pest species, active materials and resistance ratios.