Hydrogen sulfide (H 2S) has recently been identified as an endogenous gaseous signaling molecule. The aim of the present study was to investigate the effect of H 2S on high glucose- (HG-) induced ADAM17 expression and sFlt-1 production in 3T3-L1 adipocytes. Firstly, we found that HG DMEM upregulated the expression of ADAM17 and production of sFlt-1 in 3T3-L1 adipocytes. Knocking down ADAM17 attenuated the effect of high glucose on sFlt-1 production in adipocytes. HG decreased the expression of CSE and 3-MST, as well as the endogenous H 2S production. Furthermore, knocking down CSE and 3-MST significantly increased ADAM17 expression and sFlt-1 production. The addition of exogenous H 2S through the administration of sodium hydrosulfide (NaHS) inhibited HG-induced upregulation of ADAM17 expression and sFlt-1 production. In conclusion, decreased expression of CSE and 3-MST and the subsequent decrease in H 2S production contribute to high glucose-induced sFlt-1 production via activating ADAM17 in adipocytes. Exogenous H 2S donor NaHS has a potential therapeutic value for diabetic vascular complications.