The aim of this study was to determine whether the interleukin-10 (IL-10) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-10 -1082 G/A, -592 C/A, -892 C/T and IL-10.R polymorphisms and RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 16 studies (19 comparisons) involving 2647 RA patients and 3383 controls were considered in the meta-analysis. Meta-analysis of the IL-10 -1082 G/A polymorphism showed no association with RA in the study subjects, or in European or Asian subjects. However, meta-analysis of the -1082 G allele in 4 studies in Hardy-Weinberg equilibrium showed a significant association with RA (OR=1.217, 95% CI=1.027-1.442, P=0.0236). In contrast, meta-analysis of the C allele, the CC genotype, and of the CC versus the AA genotype of the IL-10 -592 C/A polymorphism showed significant associations with RA. The overall ORs of the associations between the C allele and RA were 0.684 and 0.758 (95% CI=0.494-0.946, P=0.022; 95% CI=0.475-1.210, P=0.045) in all study subjects and Asians. Meta-analysis of the CC+CT versus TT genotype and of the CC versus TT genotype of the IL-10 -892 C/T polymorphism revealed significant associations with RA. The overall OR of the association between the C allele carrier and RA was 0.552 (95% CI=0.375-0.812, P=0.003). No association was found between the IL10.R2 alleles and RA. This meta-analysis suggests that the IL-10 -592 C/A polymorphism confers susceptibility to RA in Asians and that the IL-10 -1082 G/A and -892 C/T polymorphisms are associated with RA susceptibility. These findings suggest the IL-10 genes confer susceptibility to RA.