Not much has been reported about the effects of hyperthyroidism and its correction on resistance vessels, and just two inconsistent studies have investigated the impacts of restored euthyroidism on vascular reactivity. In this regard, we designed the current study to evaluate the vascular reactivity of the mesenteric arteries of hyperthyroid and restore euthyroid rats. Hyperthyroidism was induced by administration of triiodothyronine (T 3 ; 300μg/kg, i.p., for 12 weeks in T 3 group). Euthyroidism was restored by administration of T 3 for 8 weeks and then T 3 +Methimazole (0.003% in drinking water) for 4 weeks (T 3 +MMI group). According to the McGregor method, vascular relaxation and contractility response were measured in response to acetylcholine or phenylephrine respectively. We found that maximal contractility response (E max ) to phenylephrine in the T 3 group was significantly decreased (P<0.001), and E max to acetylcholine was significantly increased compared with the saline group (P<0.05). When N G -nitro-L-arginine methyl ester (L-NAME, 3×10 −4 M) was used, E max to acetylcholine in the T 3 group was still higher than the saline group (P<0.05). However, decrease in maximal response of the T 3 group was significantly greater than the saline group (P<0.01). We also showed that when euthyroidism is restored by methimazole therapy, enhanced acetylcholine-induced vasorelaxation and impaired contractility response to phenylephrine were normalized, as there was no significant difference in E max of the T 3 +MMI group versus the saline group (P>0.05). In conclusion, synthesis of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in mesenteric arteries significantly increased as a consequence of hyperthyroidism, and this abnormal vascular reactivity is corrected by methimazole therapy.