The aim of this study was to investigate the effect of perfluorocarbon on the respiratory status of newborn mice with pulmonary hypoplasia without diaphragmatic defects, following intrauterine exposure to nitrofen. Three groups of newborn mice were compared: pups exposed to nitrofen antenatally without (group A) or with (group B) perfluorocarbon treatment and pups not exposed to nitrofen as a control (group C). Respiratory evaluation was performed by scoring, pressure-volume analysis, and histological examination. At 40 minutes after birth, the survival rates in groups A, B, and C were 51%, 94%, and 95%, respectively. The clinical scores of group B mice at 40 minutes were significantly better than those of group A mice in which pulmonary hypoplasia was induced. In group B, the hysteresis ratio was significantly higher than that in group A, and lung histology showed a significant increase in airspace. An immunohistochemical examination showed that perfluorocarbon did not alter the expression of mature surfactant protein B and surfactant proprotein C. This study demonstrated that treatment with perfluorocarbon was useful in stabilizing critically ill mice with primary pulmonary hypoplasia during the early phase of therapy.