The habitat of Drosophila melanogaster is the environment of fruit decay/fermentation which emits high concentrations of chemicals. Our recent studies revealed that D. melanogaster has been evolutionarily adapted to its habitat through tolerance to chemicals and induction of antimicrobial peptides (AMPs) plays an important role for chemical tolerance. To determine the correlation between AMPs and the chemical tolerance pathway, we hypothesized that expression of AMPs is induced by tissue damages or ROS caused by chemical exposure and AMPs activate antioxidant enzymes, thereby inducing chemical tolerance in D. melanogaster. Therefore, in this study, we investigated the induction levels of genes associated with necrosis (EGR and BSK), apoptosis (Dronc, Dcp1, and Drice), antioxidant physiology (SOD1, SOD2, CAT, Trxr1, GstD2, and GstD5), and SAM metabolism (Gnmt and Foxo) in D. melanogaster exposed to three chemicals, 2-phenylethanol, ethanol, and acetic acid. As a result, above genes were induced in chemical-exposed fly, and this supports our hypothesis of chemical tolerance pathway in D. melanogaster.