The potential impact of human leukocyte antigen(HLA) genotype variations on development of diabetic peripheral neuropathy(DPN) is not well determined.This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes(T2D) patients.Totally 106 T2 D patients,49 with DPN and 57 without DPN,and 100 ethnic-matched healthy controls were analyzed.Both groups of the patients were matched based on sex,age,body mass index(BMI) and duration of T2 D.Polyneuropathy was diagnosed using electrodiagnostic methods.HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers(PCR-SSP) method.T2 D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group(P = 0.04).HLA-DQB1*O2 allele and HLA-DRB1*O7-DQB1*O2 haplotype were associated with a decreased risk for developing DPN in T2 D patients(P = 0.02 and P = 0.05 respectively).Also,patients with severe neuropathy showed higher frequencies of DRB1*O7(P = 0.003) and DQB1*O2(P = 0.02) alleles than those with mild-to-moderate form of neuropathy.The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls.Our findings implicate a possible protective role of HLA-DQB1*O2 allele and HLA-DRB1*O7-DQB1*O2 haplotype against development of peripheral neuropathy in T2 D patients.Therefore,variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2 D patients. The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed.Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2 D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. 2 D patients with DPN showed higher frequencies of HLA-DRB1 * 10 and DRB1 * HLA-DQB1 * O2 allele and HLA-DRB1 * O7-DQB1 * O2 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed h igher frequencies of DRB1 * O7 (P = 0.003) and DQB1 * O2 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1 * O2 allele and HLA-DRB1 * O7-DQB1 * O2 haplotype against development of peripheral neuropathy in T2 D patients. Beforefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.