Background. RAGE, a multi-ligand transmembrane glycoprotein transduces biological signals associated with chronic cellular stress, and chronic and degenerative diseases. sRAGE is a variant of RAGE derived from cell surface cleavage mechanisms that might inhibit RAGE activity. Polymorphisms -374T/A (rs1800624) and -429T/C (rs1800625) in RAGE gene could be responsible for disease development, however, there have been conflicting findings. We evaluated -374T/A and -429T/C polymorphisms and measured serum sRAGE levels in Mexican population with MS. Methods. According to the harmonized criteria for the MS, 80 healthy men without any component of the MS, and 80 men with the MS were included. -374T/A and -429T/C polymorphisms of RAGE gene were genotyped by RT-PCR. sRAGE in serum was measured with an ELISA kit. Results. The studied population complied with the Hardy-Weinberg equilibrium (-374T/A p=0.58, -429T/C p=0.79). Differences were observed in all the components of the MS between MS vs. healthy subjects (p<0.000), but not according to their genotype (-374T/A p=0.57, -429T/C p=0.59). There were no differences in accordance to the genotype in glucose (p=0.22 and p=0.57), triglycerides (p=0.99 and p=0.69), cHDL (p=0.88 and p=0.77) levels, or waist circumference (p=0.84 and p=0.99 for -374T/A and -429T/C respectively). No association of MS with the -374T/A nor 429T/C polymorphism was found. There were no differences between groups in circulating sRAGE levels (p=0.132). Conclusion. -374T/A and -429T/C polymorphisms of RAGE gene are not associated with the MS in Mexican population, and have no influence on serum sRAGE levels. Gender could influence the development of the MS.