Abstract: Objective To investigate the effects of phytoestrogen α-zearalanol (α-ZAL) on vascular function in ovariectomized hyperhomocysteinemic rats. Methods Hyperhomocysteinemia was induced by fed with high-methionine diet. 40 adult female Wistar rats were assigned randomly into 5 groups: (1) Control (Con); (2) 2.5%Methionine (Met); (3) Ovariectomy+2.5%Methionine (OVX+Met); (4) Ovariectomy+2.5%Methionine+α-ZAL (OVX+Met+α-ZAL); (5) Ovariectomy+2.5% Methionine + 17β- estradiol (OVX+Met+17β-E2). 12 weeks later, blood was collected to analyze plasma estradiol and Hcy levels. Thoracic aortas were isolated to detect the response to phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP). Results The plasma Hcy levels were elevated in all rats fed with 2.5% methionine diets, especially in the OVX+Met group. In a dose-dependent manner, PE elicited significantly greater contraction in thoracic aorta rings taken from rats of OVX+Met than that taken from other groups and ACh elicited significantly less percentage relaxation in thoracic aorta rings. There was no significant difference in response to SNP between groups. Conclusion α-ZAL could remarkably improve vascular function in ovariectomized HHcy rats via attenuating elevation of plasma Hcy and endothelial cells damage, which is similar to 17β-E2.