Azadirachtin, an insect growth disruptor, is known to be an antagonist of the juvenile hormone and 20-hydroxyecdysone (20E). However, its mechanism of action remains to be understood. Furthermore, the effects of the interaction of azadirachtin and 20E have not been investigated. The current study examined the effect of azadirachtin topically applied alone or in combination with 20E on Drosophila melanogaster Meigen, 1830 (Diptera: Drosophilidae). In initial bioassays, various doses (0.5, 1, 1.5, 2.5 and 4.5 µg) of azadirachtin was tested alone on newly ecdysed pupae and the inhibition doses (ID) of adult emergence determined. In a follow-up experiment, azadirachtin applied alone at its ID₂₅ (0.59 µg) and ID50 (1.10 µg) was evaluated on catalase (CAT) and glutathion S-transferase (GST) activities, and yolk protein content in fat body and ovaries. Results showed that azadirachtin at the two tested doses increased significantly the activity of both GST at 48 and 72 hours, and CAT at 24, 48 and 72 hours following treatment. Moreover, azadirachtin treatment at these doses reduced significantly the yolk protein content in fat body and ovaries as compared to the control series. Finally, the exogenous 20E (0.25 and 0.50 µg), applied 24 or 48 h after azadirachtin treatment, relatively restored the normal values of CAT, GST and yolk protein content in fat body and ovaries. All these results indicate that exogenous 20E can compensate the depressive effects induced by azadirachtin on D. melanogaster.