OBJECTIVE: To study the effects of alprostadil on the expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in human pulmonary microvascular endothelial cells (HPMECs) with hypoxia-induced injury. METHODS: HPMECs were divided into group A (normal cultural environment), group B (3%O2), group C (3%O2+15 μg/L alprostadil) and group D (3%O2+45 μg/L alprostadil) for 24 h culture. Cell morphology was observed; MTT method was conducted to detect cell activity (recorded by absorbance); flow cytometry was adopted to detect apoptosis rate; Western blot was used to detect relative expressions of VEGF and eNOS in cells. RESULTS: Cell density in group A and D was relatively high, that in group B and C was low. Compared with group A, cell activities decreased and apoptosis rates increased in group B, C and D, expressions of VEGF and eNOS enhanced, eNOS/VEGF decreased (P<0.05). Compared with group B, cell activities increased in group C and D, VEGF expression decreased (P<0.05); apoptosis rate in group D decreased, eNOS expression decreased and eNOS/VEGF increased. Compared with group C, cell apoptosis rate was decreased in group D, VEGF expression decreased and eNOS/VEGF increased (P<0.05). CONCLUSIONS: Alprostadil maybe play effect on HPMECs with hypoxia-induced injury by up-regulating the expression level of eNOS/VEGF.