Objective: To investigate the contribution of placental leptin to the serum levels in preeclampsia and the effect of hypoxia on synthesis of placental leptin. Methods: Fifteen preeclamptic women and 20 normotensive pregnant women were recruited in present study. Leptin concentrations in peripheral venous blood samples and uterine venous blood samples were measured by radioimmunoassay. Eight cases of normal human term placental villi were cultured either in normaxia (21%O2) or in hypoxia (2%O2) followed by determining leptin in the culture medium by radioimmunoassay. Results: Leptin concentrations were significantly higher in preeclamptic women than in normotensive pregnant women, both in the peripheral vein ([23.29±12.87] μg/L vs [13.87±5.57] μg/L, P<0.01) and uterine vein ([16.44±8.62] μg/L vs [11.21±4.20] μg/L, P<0.05). Leptin concentrations were significantly higher in the peripheral vein than in uterine vein, both in the preeclamptic (P<0.01) and in normotensive pregnant women (P<0.01). Concentrations of leptin in the culture medium were significantly increased in hypoxia than in normoxia (P<0.05). Conclusion: The pathogenesis of preeclampsia may be associated with an increase of matal serum leptin and placenta leptin, and hypoxia in placenta may be an important factor that results in preeclamptic placenta to produce more leptin. Placenta is not the principal source of the serum leptin in the preeclamptic women or normotensive pregnant women.