Acetylcholinesterase (AChE) is an enzyme for hydrolyzing neurotransmitter acetylcholine. Soluble form of AChE is generated via alternative splicing and functions as a bioscavenger in Dropsophila melanogaster. In this study, effects of ethanol and acetic acid on the soluble AChE expression were investigated. Treatment of ethanol and acetic acid results in over-expression of soluble AChE in the abdomen in a dose-dependent manner. However, no apparent change in AChE expression was observed in the head. Our finding suggests that the soluble AChE is involved in chemical defense against high concentration of ethanol, which is a common by-product from fermented food,and acetic acid, the main metabolite of ethanol. Thus, high level of ethanol and acetic acid resistance in D. melanogaster appears to be evolved via the induction mechanism of soluble AChE expression.