Previous studies confirmed that the methanolic extract from Curcuma longa L. (CLME) lowers arterial blood pressure and heart rate in rats due to the blockade of extracellular Ca²⁺ influx. The aim of this study was to investigate the involvement of Na⁺-Ca ²⁺ exchanger in the vasorelaxant effects elicited by CLME in isolated rat superior mesenteric arteries. CLME (1-1,000 μg/ml) concentration-dependently relaxed phenylephrine (PHE) (10 μM) pre-contracted arterial rings with intact-endothelium (pD₂ and E_max = 2.04 ± 0.06 and 88.3 ± 3.2%) or denuded-endothelium (pD₂ and E_max = 2.06 ± 0.03 and 91.4 ± 1.0%), respectively, suggesting that the removal of endothelium has no significant effect (P>0.05) on the vasorelaxation induced by CLME. Furthermore, CLME (30, 100 and 300 μg/ml) inhibited the cumulative concentration-response curves to PHE (10^-8-10^-5 M) in a concentration-dependent manner, whereas, treatment with ouabain 100 μM (selective blocker of Na⁺-K⁺ ATPase) has no effect on the relaxant responses of CLME. However, treatment with nickel chloride (NiCl₂) (100, 300 and 400 μM), a putative Na⁺-Ca²⁺ exchanger inhibitor, concentration-dependently reduced the vasorelaxant responses of CLME. Precisely, NiCl₂ at 100, 300 and 400 μM significantly (P<0.05) decreased the pD₂ and E_max values of CLME (1.86 ± 0.03 and 81.3 ± 1.2%, 1.77 ± 0.03 and 60.2 ± 0.8%, 1.69 ± 0.04 and 55.3 ± 1.6%, respectively). Also, CLME (100 μg/ml) produced less relaxant effect with decreasing extracellular Na⁺ concentration. CLME-induced vasorelaxation was completely abolished in a Na⁺-free Tyrode's solution, a condition that eliminates the influence of the forward mode of the exchanger. The results provide indirect evidence that the stimulation of the forward mode of Na⁺-Ca ²⁺ exchanger may probably contribute to the vasorelaxation induced by CLME in endothelium-denuded arterial rings.