Interleukin-6 (IL-6) is a key pleiotropic cytokine that modulates the inflammatory response. Single-nucleotide polymorphisms (SNPs) within associated genes may contribute to the metabolic syndrome (MES). We examined the role of the IL-6 (rs1524107-C/T) and IL-6 receptor (IL-6R, rs8192284-A/C, Asp358Ala) SNPs in modulating IL-6 levels and the syndrome. A total of 1,979 older Chinese subjects aged 50-92 years from Guangzhou Biobank Cohort Study (GBCS) were recruited. SNPs were detected using Taqman SNP genotyping kits. IL-6 was measured using enzyme-linked immunosorbent assay. The genotype frequencies were 4.9, 33.9, and 61.3% for the IL-6 CC, CT, and TT, and 12.0, 44.9, and 43.1% for the IL-6R CC, AC, and AA, respectively. Both SNPs were in Hardy-Weinberg equilibrium. The IL-6 SNP was not associated with IL-6 levels or the MES, but was dose-dependently associated with fibrinogen levels, P = 0.049. IL-6 levels significantly decreased with increasing proportions of the IL-6R A-allele 9.8 +/- 4.9, 9.3 +/- 4.8, and 8.4 +/- 4.3, respectively, P = 0.001. Conversely, the A-allele was associated with elevated triglyceride, P = 0.009, C-reactive protein, P = 0.047, and potentially with fasting glucose levels, P = 0.077. There was an increasing prevalence of the MES in those carrying the IL-6R CC, AC, and AA genotypes at 18.1, 21.5, 25.2%, respectively, P = 0.010. The SNP was a significant independent predictor of the MES after adjusting for general obesity, age, gender and lifestyle, and socioeconomic parameters, P = 0.023. These data, which are in accord with studies from white populations suggest the IL-6R SNP may play a role in the pathogenesis of the MES possibly through modulating IL-6 levels.