We studied single nucleotide polymorphisms (SNPs) and haplotypes in the urotensin-II (UTS2) and urotensin-II receptor gene (UTS2R) in Hong Kong Chinese (224 hypertensive and 306 normotensive unrelated subjects) and their relation to hypertension and the metabolic syndrome. For UTS2, the GGT haplotype (−605G, 143G and 3836T) was associated with higher plasma level of U-II and insulin, and higher homeostasis model assessment of insulin resistance index and β-cell function. For UTS2R, the AC haplotype (−11640A and −8515C) was associated with higher 2h plasma glucose after a 75g oral glucose load. Therefore, U-II and its receptor may play a role in insulin resistance.