The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus …