Repetitive applications of drugs to tumor tissues and animals induced resistance and/or tolerances which caused severe problem in agriculture and medicine. However, we still do not clearly understand the molecular and cellular mechanisms underlying development of resistance and tolerance to chemicals. Drosophila is one of the most widely used model for studying fundamental phenomena in sciences using its available genetic and genomic resources. To investigate unknown molecular and cellular basis of drug resistance development, we applied Drosophila with two different concentrations of a chemical after treating them with Ethyl methanesulfonate mutatgenesis. We found that flies treating with two different concentration of chemicals showed different susceptibility to a chemical. We have established two different lines showing different susceptibility to a chemical. We will use these lines to compare any differences in mRNA expression profiling and enzyme activities. (This work was supported by project title: Investigation on cross drug resistance mechanisms using Drosophila as a model (PJ010821032016) from Rural Development Administration).