Variants of the interleukin-1β gene (IL1B) are implicated in the development of diabetic nephropathy (DN). The present candidate-gene association study was conducted to investigate the association between the IL1B C-511T variant and the risk of DN in a Caucasian population. The study population consisted of 173 cases (patients with type 2 diabetes mellitus [DM] and DN) and 186 controls (patients with DM free of DN). Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The PCR product was a 304-bp long DNA fragment of the IL1B gene promoter region, extending from position -702 to -398 and including the polymorphic AvaI site (at position -511). The magnitude of the overall association was tested using the generalized odds ratio (ORG) metric, a genetic model-free approach. The ORs (adjusted for effect modifiers) of the additive and co-dominant models were also estimated. The mode of inheritance was assessed using the degree of dominance index (h). There was a significant difference in the genotype distribution between the group of cases with DN compared with diseased controls free of DN (p=0.014). Analysis produced a significant ORG (ORG=1.74, 95% confidence interval [CI]=1.20-2.52), indicating that the risk of DN is significantly associated with the mutational load. The risk of developing DN is significantly enhanced in IL1B T allele carriers (dominant model, p=0.005) and in homozygotes (additive model, p=0.018) respectively. However, the recessive model for T allele (p=0.097) and the co-dominant model (p=0.085) produced non-significant results. Considering that the additive model was significant (OR=2.53, 95% CI=1.20-5.36) and the co-dominant is non-significant (OR=1.53, 95% CI=0.97-2.40), the mode of inheritance is complete "additiveness," with the degree of dominance being h=0. The findings provided evidence that the IL1B C-511T variant might be associated with development of DN.