*Objective:* Type 2 Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and with a major feature of insulin resistance. Genetic association studies have suggested that _ENPP1_ might play a potential role in susceptibility to type 2 diabetes and obesity. Our study aimed to examine the association between _ENPP1_ and type 2 diabetes and obesity.

*Design:* Association study between two SNPs, rs1044498 (K121Q) and rs7754561 of ENPP1 and diabetes and obesity in the Chinese Han population.

*Subjects:* 1912 unrelated patients (785 male and 1127 female with a mean age 63.8 ± 9 years), 236 IFG/IGT subjects (83 male and 153 female with a mean age 64 ± 9 years) and 2041 controls (635 male and 1406 female with a mean age 58 ± 9 years).
 
*Measurements:* Subjects were genotyped for two SNPs using TaqMan technology on an ABI7900 system and tested by regression analysis.

*Results:* By logistic regression analysis, rs1044498 (K121Q) and rs7754561 showed no statistical association with type 2 diabetes, obesity under additive, dominant and recessive models either before or after adjusting for sex and age. Haplotype analysis found a marginal association of haplotype C-G (p=0.05) which was reported in the previous study.

*Conclusion:* Our investigation did not replicated the positive association found previously and suggested that the polymorphisms of _ENPP1_ might not play a major role in the susceptibility to type 2 diabetes or obesity in the Chinese Han population
