Abstract: Objective To observe theexpression variations of estrogen receptor alpha (ERα) in different periods of mice offspring and the gender-dependent differences in the lung tissue with parental arsenic exposure. Methods Parental female mice were exposed to arsenic by gavage from gestational day 8th to offspring infancy, and offspring were exposed to arsenic by drinking water after infancy. The expression level of \ERα mRNA and protein in lung tissue of the male and female offspring in different developmental periods and different doses (low, middle, high) of sodium arsenite exposure were detected by real-time PCR and Western blot. Results \ERα mRNA expression in female lung tissue was lower than male in embryonic period (\P\ERα mRNA expression in female lung tissue was higher than that of male in infant and adult periods (middle dose of infancy \P\P\ERα mRNA expression in female lung tissue of infancy and adulthood was higher than that in embryonic period (low, middle and high dose groups \P\ERα protein expression in arsenic exposed female lung tissue was higher than that of male in infant and adult periods, it was also increased by compared with corresponding control groups (\P\ERα protein in exposed adult female and male offspring were higher than that of infancy. Conclusion Arsenic infected during pregnancy can increase the lung tissue’s \ERα expression level of female offspring in infancy and adulthood. This result is significant to elucidate the role of environment pollutants in gender difference of lung cancer’s occurrence.