Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions, including insulin secretion. An insertion/deletion (I/D) polymorphism of the alpha2B-AR gene located on chromosome 2 has recently been described. The aim of the present study was to examine if there is a difference in the D allele frequency of alpha2B-AR gene between type 2 diabetic patients and controls, as well as to ascertain whether the D allele confers an increased risk for earlier onset of diabetes. This study included 199 type 2 diabetic patients and 204 age- and sex-matched healthy volunteers. Genotyping of I/D polymorphism was performed by PCR. No significant difference in the D allele frequency was observed between the two groups (22.1% vs. 19.1%, p = 0.409). Among type 2 diabetic patients, however, presence of the D allele was associated with significantly younger age at onset of diabetes (51.4+/-8.6 vs. 59.2+/-9.7 years, p < 0.001). Multiple stepwise linear regression identified alpha2B I/D genotype as an independent predictor of age at onset of DMT2, explaining 14.3% of its variance. This result indicates that the D allele may be implicated in impaired glucose metabolism leading to earlier manifestation of diabetes in predisposed subjects.