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Three recent meta-analyses regarding TNF-alpha-238, -308 polymorphisms, and diabetes have been published, which reported that TNF-alpha-238, -308 polymorphisms were not associated with type 2 diabetes mellitus (T2DM); however, TNF-alpha-308 polymorphism was positively associated with type 1 diabetes (T1DM) [1–3]. These findings were interesting but complicated. Several points should be further discussed on these findings. First, it has been still unclear whether these two single nucleotide polymorphisms (SNPs) could lead to a higher or lower TNF-alpha production in the human beings, although the in vitro experiments results reported that these SNPs regulated the TNF-alpha expression. Seldom population study reported the differences of TNF-alpha between the genotypes of the SNPs. It is important for readers to know whether these SNPs could regulate TNF-alpha secretion in human beings. The determination of TNF-alpha in patients with diabetes with various genotypes of these SNPs could provide readers more information about their roles in the development of diabetes. Second, a positive association between TNF-alpha and T1DM suggested us that this SNP might exert its role by interacting with other genetic factors in the T1DM development. Previous studies have reported strong linkage disequilibriums between HLA DR3, HLA-DRB1*0301 alleles, and TNF-alpha-308 polymorphism [1, 4], indicating that this significant association of TNF-alpha-308 polymorphism may not be independent. TNF-alpha-308 polymorphism might be only a participant in the whole genetic pathopoiesis of T1DM. Larger range of loci should be considered regarding the interaction between them. Third, another meta-analysis reported that TNF-alpha308 polymorphism was associated with metabolic syndrome, and a large-scale study also suggested that smaller effect of this SNP might exist [5, 6], which suggested that TNF-alpha-308 polymorphism might play a role in the development of metabolic disorder; however, its mild effect could not cause T2DM.