Using biochemical and molecular assays, we identified distinct patterns of detoxification enzyme activity in insecticide resistance in field populations of Bactrocera zonata (Saunders) which suggested that certain enzymes are involved in developing resistance. Field populations of B. zonata showed increased activity of detoxifying enzymes compared with susceptible populations. Correlation analysis showed that enzyme activity was positively correlated with resistance to malathion, lambda-cyhalothrin, imidacloprid and spinosyn. However, an inverse correlation between enzyme activity and methomyl resistance has been found. The results showed that the synergists of PBO and Sesamex had good inhibitory activity on detoxifying enzymes, with the highest inhibitory potency on monooxygenases. These results showed that pesticides should be used judiciously and in prescribed ways to integrate pesticides into IPM programs of B. zonata.