Exposure to mercury is known to increase cardiovascular risk but the underlying mechanisms are not well explored. The present study was undertaken to investigate the modulatory role of mercury on vascular function and to elucidate the mechanisms behind the observed effects. Thoracic aorta from Wistar rats (300g, n=50) treated with either perse mercury chloride (10-9M, 10-5M) or methyl mercury chloride (10-9M, 10-5M) or acutely mercury chloride (single dose of 5 mg/kg; ip (1)) or methyl mercury chloride (single dose of 5 mg/kg; po (2)) or chronically mercury chloride (1.25×10-6 M/L in drinking water for 30 days (3)) or methyl mercury chloride (0.5 mg/kg /day, orally for 30 days (2)) were used. Experiments were performed in accordance with recommendations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Govt. of India. Zero mortality was observed and there was no change in mean body weight after 30 days. Decreased acetylcholine (ACh) induced vasodilatation in perse mercury chloride (10-5M; R max; (52.7±2.8%:08.2±1.2%*), methyl mercury chloride (10-5M; R max; (52.7±2.8%:11.5±2.9%*), acutely mercury chloride (R max; (52.7±2.8%:36.1±2.2%*), chronically mercury chloride (R max; (52.7±2.8%:26.3 ±1.2%*) and methyl mercury chloride (R max; (52.7±2.8%:34.8±2.1%*) exposed rats was observed suggesting endothelial dysfunction. However, an increased ACh induced vasodilation was observed in perse mercury chloride (10-9M, R max; (52.7±2.8%:73.9±1.8%*), methyl mercury chloride (10-9M; (52.7±2.8%:79.29±1.3%*)) and acutely methyl mercury chloride (R max; (52.7±2.8%:70.4±2.9%*), exposed rats indicating modulation of the endothelial function. The superoxide anion scavenger SOD + catalase augmented the ACh responses in vessels from mercury-treated rats suggesting mercury induces oxidative stress (Fig.1). The NOS inhibitor, L-NAME significantly reduced the ACh induced vasodilatation in perse mercury chloride (10-9M), methyl mercury chloride (10-9M) and acutely methyl mercury chloride, in comparison to mercury chloride (10-5M), methyl mercury chloride (10-5M), acutely mercury chloride, chronically mercury chloride and methyl mercury chloride exposed rats exposed rats suggesting that mercury may induce increased/decreased production of NO depending on the dose, form and type of exposure (Fig.2). Increased MDA levels were accompanied with increase in serum NO levels in all the mercury treated rats suggesting that mercury causes oxidative stress and increased production of NO. A delicate balance exists between free radicals and NO released by endothelial cells on mercury exposure. When there is an increase in NO release, enhanced endothelial function is observed. When the balance is tipped in favor of oxidative stress, endothelial dysfunction is observed. The form of mercury, route, dose and period of exposure, play an important role in determining the harmful effect of mercury on the vascular endothelium. Therefore NO signaling mechanism and oxidative stress play an important function in the mercury-induced cardiovascular diseases in the populations exposed to mercury. *p < 0.05