Imbalance release of proangiogenic and antiangiogenic factor from placenta causes maternal endothelial dysfunction which is main manifestation of preeclampsia(PE). Hydrogen sulfide (H2S) “the third endogenous gaseous signaling transmitter”, has been shown to have a pro‐angiogenic effect. We investigated whether H2S modulate the release of proangiogenic and antiangiogenic factors in human placentas. It was found that H2S synthesis enzymes cystathionine β‐synthase(CBS) and cystathionine γ‐lyase(CSE) were expressed in human placenta. The levels of CBS and CSE positively correlated with the levels of agiogenic factor vascular endothelial growth factor(VEGF) and inversely correlated to antiangiogenic factor soluble fms‐like tyrosine kinase 1(sFlt‐1) in placentas. H2S precursor L‐cysteine significantly increased VEGFA release whereas decreased sFlt‐1 release in cultured placental explants andd placental trophoblasts. The effects of H2S precursor could be reversed by siRNA of CBS and CSE. Moreover, H2S decreased miR‐200c which target VEGF and increased miR‐133b which target sFlt‐1. The level of miR‐200c was significantly increased whereas miR‐133b decreased in PE placentas. Our results suggest that H2S is an important factor that maintains the balance of proangiogenic factor VEGFA and antiangiogenic factor sFlt‐1 in placenta. Reduced H2S generation in placentas leads to imbalance release of proangiogenic and antiangiogenic factor from placenta.Grant Funding Source: Natural Science Fundation of China No.81370734