Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions in humans. An insertion/deletion (I/D) polymorphism of the alpha2B-AR gene located on chromosome 2 has been described. The aim of the present study was to investigate the potential association between alpha2B gene I/D polymorphism and peripheral neuropathy in Greek patients with type 2 diabetes mellitus. The study included 130 patients (70 men) with diabetic neuropathy (group A) and 60 patients (34 men) without diabetic neuropathy (group B). There was no difference in age, gender and diabetes duration between the groups. Diabetic neuropathy was diagnosed by clinical examination using the Diabetic Neuropathy Index (DNI). Genotyping of I/D polymorphism was performed by PCR. Frequency of the D allele was significantly higher (p=0.001) in group A (26.9%) as compared to group B (11.7%). DNI score differed significantly (p=0.001) between the three genotype groups (I/I, I/D, D/D). It was significantly higher (p=0.04) in patients with I/D (3.7+/-1) than in those with I/I (2.5+/-0.9) and significantly higher (p=0.001) in patients with D/D (5.6+/-1.3) than in those with I/D (3.7+/-1).Patients with neuropathy exhibit a significantly higher frequency of the D allele in comparison to those without neuropathy. Presence of the D allele is also associated with a higher neuropathic score. These results provide evidence for an association of the D allele with both presence and severity of neuropathy in patients with type 2 diabetes mellitus.