During early pregnancy, an environment of relative low oxygen tension is essential for normal embryonic and placental vasculature. In low-oxygen conditions, the hypoxic-inducible factor-1 (HIF-1), composed of α and β subunits, controls the expression of a number of genes such as vascular endothelial growth factor (VEGF), a key angiogenic factor. The recent studies in some tumor cells have found that the labile component, HIF-1α, is not only activated by hypoxia but also by peptides such as interleukin-1 (IL-1) in normoxia. In this article, we demonstrated that exposure of normal human cytotrophoblast cells to IL-1β stimulated the expression of HIF-1α protein. Meanwhile, IL-1β also induced the secretion of VEGF in normal human cytotrophoblast cells. Our data indicated that IL-1β induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Moreover, treatment of cells with PD98059, an inhibitor of ERK1/2 signaling, inhibited the stimulation of HIF-1α protein expression and VEGF secretion by IL-1β. These data indicate that, in normal human cytotrophoblast cells, IL-1β induces HIF- 1α-mediated VEGF secretion and that IL-1β-stimulated ERK1/2 activation may be involved in this process.