Arsenic exposure is considered as a risk factor for lung cancer. However, toxic effects of the metabolic mechanism responsible for arsenic-induced toxicity and especially chronic effects, are less known. Here we constructed a cell model of lung adenocarcinoma A549 cells by chronic arsenic exposure. Cell-based experiments showed that A549 cells display platinum resistance with chronic exposure of arsenic. The metabolic response of A549 cells to arsenic exposure was profiled by gas chromatography-mass spectrometry.