Objective To explore the effects of dimethyl fumarate（DMF）on hydrogen peroxide（H2O2）⁃ induced ferroptosis of human cardiac microvascular endothelial cells （HCMEC） and its potential mechanism. Methods HCMEC were cultured in vitro，incubated with H2O2，and then treated with different concentrations of DMF. Cell proliferation was measured by CCK ⁃ 8 method. The level of cell inflammation was detected by ELISA. Western blot was used to detect the changes of ferroptosis⁃related proteins GPX4 and ACSL4，as well as Nrf2/HO⁃1 and JAK2/STAT1 pathway proteins. Results The results of CCK8 assay showed that compared those in the control group，H2O2 significantly inhibited the proliferation of HCMEC cells，whereas，DMF treatment promoted H2O2 ⁃ induced cell proliferation in a concentration dependent manner（P < 0.05 for all）. H2O2⁃induced increased levels of inflammatory cytokines TNF⁃α，IL⁃1β and IL⁃18 in HCMEC cells were reversed by DMF treatment（P < 0.05）. Western blot revealed that H2O2 treatment caused the decrease in GPX4 protein and increase in ACSL4 protein； whereas DMF inhibited ferroptosis of HCMEC cells induced by H2O2（P < 0.05）. In addition，H2O2 induced a decrease in Nrf2 and HO⁃1 expression，while an increase in JAK2 and STAT1 phosphorylation levels in HCMEC （P < 0.05）. Compared with those in the H2O2 group，DMF increased Nrf2 and HO⁃1 proteins and down⁃regulated the phosphorylation levels of JAK2 and STAT1（P < 0.05）. Finally，it was found that Nrf2 inhibitor ML385 signifi⁃ cantly weakened the inhibition of ferroptosis and the protective effect of HCMEC damage. Conclusion DMF inhib⁃ its H2O2 ⁃induced inflammation of HCMEC and ferroptosis. Nrf2/HO⁃1 and JAK2/STAT1 pathways may play a key role in DMF⁃mediated protection of HCMEC.