Abstract: The aim of the present study was to investigate the effects of curcumin and Tetra Hydro Curcumin (THC) on the inhibition of endothelium-dependent vasorelaxation of the isolated rat aorta by Homocysteine Thiolactone (HTL). Carbachol, an endothelium-dependent vasodilator, caused concentration-dependent vasorelaxation in rat aortic rings. Exposure of aortic rings to HTL (0.3 and 1 mM) for 90 min significantly inhibited endothelium-dependent vasorelaxation to carbachol. In addition, contractions induced by methoxamine were significantly reduced after pretreatment with 3 mM HTL. Curcumin (10 and 30 μM) significantly restored carbachol-induced vasorelaxation inhibited by HTL (1 mM). Similar effects were observed after pretreatment of aortic rings with THC (10 and 30 μM). Moreover, HTL-induced impairment of vasorelaxation to carbachol could be blocked by either L-arginine (3 mM), a precursor of nitric oxide or superoxide dismutase (SOD, 200 U mL-1), a scavenger of superoxide anion. These results demonstrate that impairment of endothelium-dependent vasorelaxation induced by HTL is due to a reduction of nitric oxide and the generation of oxygen free radicals. Interestingly, curcumin and THC could restore endothelial dysfunction induced by HTL which may be related to their antioxidant properties. The present study provides pharmacological data to support the hypothesis that curcumin and THC have vasoprotective effects in hyperhomocysteinemia.