Formaldehyde (FA), a common environmental pollutant, has toxic effects on central nervous system.The detailed mechanism of FA neurotoxicity has not been fully elucidated.In this study, we found that C/EBP homologous protein (CHOP) expression, a biomarker of endoplasmic reticulum (ER) stress, was increased and pro-caspase-12 was decreased after PC12 ceils exposure to FA.These results suggest that FA actually induces ER stress.Thioredoxin-1 (Trx-1) has various biologic activities, including the control of redox balance, the modulation of ER stress and inhibition of apoptosis.In the present study, Trx-1 expression was increased by FA at early stage, but decreased at late stage.Ginsenoside Rgl had the potential to induce Trx-1 expression and attenuated FA-induced neurotoxicity.ER stress caused by FA was suppressed by ginsenoside Rgl.These data indicate that Trx-1 is a therapeutic candidate for treating against FA-induced neurotoxic effect.