Abstract: Objective To investigate the effects of Tetrandrine（TET） prenatal intervention on the differentiation of alveolar epithelial cells type Ⅰ (AECⅠ) in rat model of Nitrofen-induced congenital diaphragmatic hernia（CDH）. Methods Timed-pregnant Sprague-Dawley rats were divided into three groups, namely control， CDH and TET group on day 9.5 of gestation. The rats in TET group and CDH group were given 125 mg of Nitrofen by gavage one time, while the rats in control group were given the same dose of seed fat. After that, the rats in TET group was given 30 mg/kg of TET by gavage once a day for three days from day 18.5 of gestation, while the rats in CDH and control group were given the same dose of normal saline. On day 21.5 of gestation, all fetuses were delivered by cesarean, the lungs of fetuses were histologically evaluated by microscope and electron microscope. The expressions of type Ⅰ cell-specific protein（RT140） and thyroid transcription factor 1（TTF1） in alveolar fluid content were analyzed by RT-PCR and immunohistochemistry staining. To detect the number of AECⅠand AECⅡof each group by transmission electron microscopy and calculate the percentage of AEC Ⅰ and AEC Ⅱ(Ⅰ/Ⅱ %). Results The microscope and electron microscope study found the lungs of fetuses in CDH group showed marked hypoplasia, in contrast to the improvement of hypoplasia in TET fetuses. The pulmonary alveolar area had significant difference statistically （ P<0.01） in each group, which present as control>TET>CDH. Ⅰ /Ⅱ % had significant difference statistically （ P<0.01） in each group, which present as control>TET>CDH. The expression level of TTF1 was up-regulated in both CDH and TET groups, and it was higher in CDH group （ P<0.01）.The expression level of RT140 were down-regulated in CDH and TET groups, which was lower in CDH group（ P<0.01）. Conclusion The development of AECⅠwas interfered in CDH rat model, TET prenatal treatment could improve the lung development of CDH.