Abstract We examined radiation effects on the relationship between diabetes development and genetic background in atomic-bomb (A-bomb) survivors. Our main aim in this study was to shed light on the role of genetic background in diabetes onset among A-bomb survivors by studying possible relationships between human leukocyte antigen (HLA) genotypes and the diabetes in patients and controls. We examined the effects of different HLA haplotypes on type 2 diabetes development by determining the DQA1 and DRB1 alleles of Hiroshima A-bomb survivors (111 diabetic patients and 774 controls) using the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. We noted an increased risk of diabetes in the higher dose group among these patients (trend p = 0.001). The risk of the most heavily exposed group was significantly higher than that of the unexposed group or the low-dose group especially in survivors with the DQA1*03-DRB1*09 or DQA1*0401-DRB1*08 haplotypes (trend p = 0.002 or p = 0.05, respectively). By contrast, in people with other haplotypes, the risk did not increase significantly with increasing dose. These results suggest that individuals with specific HLA haplotypes may have an increased risk of diabetes with increased-dose categories.