BACKGROUND Maternal nicotine exposure induces lung injuries and fibrosis in rat offspring. Epithelial-mesenchymal transition (EMT) following lung injury is a process in which epithelial cells mediate tissue repair. OBJECTIVE To determine the effects of maternal nicotine exposure on EMT in neonatal rat lungs. METHODS Nicotine was administered to pregnant Sprague-Dawley rats using a subcutaneous osmotic minipump that delivered a dose of 6 mg/kg/day on gestational days 7-21 or from gestational day 7 to postnatal day 14. A control group received an equal volume of saline. RESULTS The percentage of 8-hydroxy-2'-deoxyguanosine-positive cells in nuclear staining was significantly higher, the E-cadherin protein expression was significantly lower, and the N-cadherin protein expression was significantly higher in rats born to prenatal and postnatal nicotine-treated dams than in those born to prenatal saline- and nicotine-treated dams on postnatal day 7. These characteristics of EMT were associated with a significant increase in α-smooth muscle actin (SMA) expression on postnatal day 21. Rats born to prenatal and postnatal nicotine-treated dams showed significantly higher α-SMA expression and total collagen than those born to prenatal saline- and nicotine-treated dams on postnatal day 21. The number of cells expressing fibroblast-specific protein 1 and vimentin was higher in rats born to prenatal and postnatal nicotine-treated dams than in those born to prenatal saline- and nicotine-treated dams on postnatal days 7 and 21. CONCLUSIONS Maternal nicotine exposure during gestation and lactation induces EMT and contributes to lung fibrosis in rat offspring.