Metabolic syndrome (MetS) is an inflammatory disorder, in which various cytokines play important role in tilting balance towards disease state. Interleukin-10 (IL-10) is an important antiinflammatory cytokine, but its genetic polymorphisms and serum levels in Indian MetS subjects are unknown. Three IL-10 gene polymorphisms (−1082A>G (rs1800896), −819C>T (rs1800872) and −592C>A (rs1800871)) were genotyped with PCR-RFLP in MetS subjects (n = 384) and age/sex matched control subjects (n = 386). Serum IL-10 was measured using enzyme-linked immunosorbent assay. Serum IL-10 level was significantly low in MetS subject and significantly correlated with clinicobiochemical parameters of MetS. Of three investigated promoter polymorphisms, IL-10 –819C> T and –592C>A were significantly associated with risk of MetS. The mutant alleles −819T and −592A of IL-10 gene polymorphism were significantly higher in MetS subjects compared to controls. Of the four different haplotypes obtained, common ACC haplotype and rare GTA haplotype of IL-10 polymorphisms were associated with MetS. The mean of fasting insulin and HOMA-IR were significantly different between the genotypes of both −819C>T and −592C>A polymorphisms of IL-10 in MetS subjects. These results suggested that polymorphisms in IL-10 gene (−819C>T and −592C>A), haplotypes (ACC and GTA) and serum level are significantly associated with risk of MetS. IL- 10 −819C>T and −592C>A polymorphic variants are also significantly associated with insulin level and homeostasis model assessment-insulin resistance in north Indian MetS subjects.