Abstract: This study is to investigate the impairment and possible mechanism of endothelium-dependent relaxation of mice mesenteric arteries induced by mmLDL. Wire myography was employed to examine endothelial function of mesenteric arteries. Ultramicrostructure of mesenteric vascular beds were detected by transmission electron microscope. The results showed that endothelium cell edema and peeling, vascular elastic membrane fracture traces in mmLDL group. Endothelium-dependent relaxation was decreased in a time- dependent and dose-dependent manner by using mmLDL, compared with normal arteries. In endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation, the R_max and pIC₅₀ were decreased from (63±5)% and 6.42±0.09 of normal saline control to (31±3)% and 5.67±0.07 in mmLDL group (P <0.001, P <0.001), respectively. In nitric oxide (NO)-mediated relaxation, the R_max and pIC₅₀ were decreased from (45±4)% and 5.93±0.08 in normal saline control to (32±4)% and 5.43±0.11 in mmLDL group (P <0.05, P <0.01), respectively. There is no significant alteration of prostacyclin I₂ (PGI₂) pathway between these two groups. In conclusion, mmLDL induced the impairment of the ultramicrostructure of mesenteric vascular endothelium cell as well as the endothelium-dependent relaxation. The latter includes the dysfunction of NO- and EDHF pathway mediated endothelium-dependent relaxation.