The aim of this study was to assess the association between G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene and the circadian variation in blood pressure, insulin sensitivity and salt sensitivity in subjects with uncomplicated, never-treated essential hypertension receiving low-, normal- and high-salt diets. The study was performed on 115 subjects aged 27.48±5.1 years with never-treated, uncomplicated hypertension. In the 7-day consecutive period of time, subjects received a normal-, low- and high-salt diet. At the end of each dietary regimen, the following parameters were recorded: 24-h blood pressure monitoring, lipid profile, insulin level, glucose level, aldosterone level and plasma renin activity. Insulin resistance was evaluated by the homeostasis model assessment (HOMA). In comparison with Gly/Gly carriers, subjects with the G972R polymorphism had higher concentrations of total and LDL cholesterol and triglycerides and HOMA but lower HDL cholesterol. On a high-salt diet, patients with the G972R polymorphism had an increased risk for insulin resistance (odds ratio (OR)=11.42, 95% confidence interval (CI) 7.68-28.44), salt sensitivity (OR=5.38, 95% CI 1.14-25.34) and non-dipper hypertension (OR=3.6, 95% CI 1.07-12.09). Regardless of the dietary salt intake, blood pressure values were similar between G972R and Gly/Gly carriers. In conclusion, the results of our study suggest that the G972R polymorphism of the IRS-1 gene is associated with insulin resistance, salt sensitivity and non-dipper hypertension.