Acetylcholinesterase (AChE) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine. Soluble form of AChE is generated via alternative splicing and functions as a bioscavenger in Dropsophila melanogaster. In this study, effects of acetic acid on the soluble AChE expression were investigated. Treatment of acetic acid resulted in over-expression of soluble AChE in the abdomen in a dose-dependent manner. The soluble AChE was determined to be expressed in the fat body. 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 acetic acid, which is a common by-product in fermenting foods. The high level of acetic acid resistance in D. melanogaster, thus, appears to have been evolved via the induction mechanism of soluble AChE expression.