Our previous study showed that endosulfan could trigger the extrinsic coagulation pathway via damaging endothelial cells and cause the hypercoagulability of blood.To investigate the mechanism of endosulfan damaging endothelial cell, human umbilical vein endothelial cells (HUVECs) were exposed to 1, 6, 12 μg/mL endosulfan, 12 μg/mL endosulfan + N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-S-Phenylglycinet-butylester (DAPT, inhibitor of Notch) (20μM) and 12 μg/mL endosulfan+ N-Acetyl-L-cysteine (NAC) (3mM) for 24 h.The results showed that endosulfan could inhibit cell viability and increase the LDH release, result in the cycle arrest of both S and G2/M phases, induce the proliferation inhibition and apoptosis in HUVECs.Endosulfan also damaged the microfilaments, microtubules, cell nuclei as well as arrested the mitosis process; remarkably increased the protein expressions of Jagged1, D114, Notch1, Cleaved-Notch1, Notch4, Hes1 and p21; significantly induced productions of the reactive oxygen species and malondialdehyde in HUVECs.While the presence of DAPT antagonized the above changes of the cycle arrest, proliferation inhibition and expressions of D114, Notch1,Cleaved-Notch1, Hes1 and p21 caused by endosulfan, NAC could attenuate the LDH release,productions of the reactive oxygen species, malondialdehyde, apoptosis and expressions of D114,Notchl, Cleaved-Notchl, Notch4 and Hesl induced by endosulfan.The results suggested that endosulfan could induce apoptosis and proliferation inhibition via the Notch signaling pathway as a result of oxidative stress.Meanwhile, endosulfan may directly lead to cell cycle arrest through damaging the cytoskeleton.