Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant widely used in industry and consumer products. Previous studies with rats suggested that gestational exposure to PFOS may affect the lung development in the offspring. The mechanism, however, is still unknown. In the present study, we have exposed 24 pregnant SD rats from gestational day 12-18 to different doses of PFOS (0, 1 or 5 mg/kg BW/day). The lungs of the offspring were analyzed at postnatal days 1, 3, 7 and 14. PFOS treatment appeared to reduce the alveolar numbers, resulting in simplified alveolar structure and thickened alveolar septa. Also, PFOS treated animals had increased lung inflammation with up-regulated inflammasome associated proteins NLRP3, ASC, Caspase-1 and GSDMD and increased inflammatory cytokines IL-18 and IL-1β. At the same time, HIF-1α and VEGFA were significantly down-regulated. Since HIF-1α and VEGFA are critical factors promoting alveolar development and pulmonary angiogenesis, these results suggested that PFOS may also affect lung development by inhibiting HIF-1α and VEGFA expression. Our results here indicate that gestational exposure to PFOS may affect lung development in the offspring with pathological characteristics similar to bronchopulmonary dysplasia (BPD), a severe lung developmental defect. The results also suggest that environmental factors such as PFOS may contribute to the increasing incidence of developmental lung diseases, such as BPD, by elevating lung inflammation and inhibiting lung development.