Alpha-2-adrenergic receptor (ADRA2A) is involved in the sympathetic nervous system and plays a role in the regulation of insulin secretion and lipolysis. Recent studies have indicated that the ADRA2A polymorphisms are associated with type 2 diabetes (T2DM) in Caucasians and African Americans. The present study aimed to evaluate the association between the ADRA2A polymorphisms and T2DM in a Chinese Han population. Two single-nucleotide polymorphisms (SNPs) rs521674 and rs553668 in the ADRA2A gene were genotyped in 2094 Chinese subjects (1042 T2DM patients and 1052 nondiabetic controls) by using the TaqMan allelic discrimination technique. A single-locus analysis indicated that SNP rs553668 was associated with T2DM (p=0.04). Further analysis indicated that the association of SNP rs553668 was found in T2DM patients with body mass index (BMI)<25 kg/m(2) (p=0.03), but not in the patients with BMI≥25 kg/m(2) (p=0.56). This association was still significant in a recessive model (p=0.01, odds ratio=0.68, 95% confidence interval=0.51-0.92). In conclusion, the present study provides evidence that the ADRA2A polymorphism, rs553668, is associated with lean T2DM patients in a Chinese Han population. Further investigation to explore the role of ADRA2A in the regulation of body weight has been taken into our consideration.