Cooking oil fumes (COFs) derived PM is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM. In conclusion, our data suggested that exposure to COFs-derived PM resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs.