Objective To explore the mechanism of pulmonary hypoplasia in case of congenital diaphragmatic hernia (CDH), and study the ultramicrostructural features of lung tissue of CDH fetal rat models at different developmental stages. Methods Seven SpragueDawley (SD) pregnant rats were randomly divided into CDH group (n=4) and control group (n=3). For the rats in the CDH group, Nitrofen was used to fill in the stomach once at day 9.5 of pregnancy (125 mg of Nitrofen dissolved in 2 ml of olive oil each), and 3, 10, 17 fetal rats were collected at day 16, 18 and 21 of pregnancy respectively. For the rats in the control group, 2 ml of olive oil was used to fill in the stomach, and 10 fetal rats were collected at day 16, 18, and 21 of pregnancy respectively. The lung tissue sections of the fetal rats collected on day 16 were observed under transmission electron microscope (TEM). For the lung tissue of the fetal rats collected on day 18, hematoxylineosin (HE) staining and TEM observation were performed and the incident of CDH was detected. Besides the procedures carried out for the rats collected on day 18, the ratio of fetal lung to body weight was observed for the lung tissue of the fetal rats collected on day 21. Results (1) The ratio of fetal lung to body weight of fetal rats in the CDH group was significantly lower than that of fetal rats in the control group (0.0238 vs. 0.0430, Plt;0.01). The incidences of CDH in the 18thday and 21stday fetal rats in the CDH group were 90.00% and 82.35%respectively, while no CDH was observed in the corresponding fetal rats in the control group, suggesting pulmonary hypoplasia in the CDH group. (2) The ultramicrostructural observation showed that compared with the control group, pulmonary hypoplasia appeared in 16thday fetal lungs in the CDH group, i.e., broad breathing barrier substrate, little contents, predominant euchromatin and rich ribosomes in the alveolar epithelial cells, and no microvilli in the bronchial lumen. The observation on the 18thday and 21stday samples suggested that, with the progressing of pregnancy, the abovementioned features became more obvious. (3) Typical lamellated body was observed in fetal lung type Ⅱ alveolar epithelial cells from the 21stday fetuses in both the CDH group and the control group, suggesting that some late subcellular structures were normal. Conclusion Lung hypoplasia develops in the early period of fetal rats with CDH rather than in the late period, implying that the treatment of pulmonary hypoplasia of diaphragmatic hernia should be performed in the early stage of lung development.