It is evident that cytokines play an important role in the pathogenesis as well as disease progression of IgA nephropathy (IgAN). Several gene polymorphisms of the pertinent cytokines have an influence on the level of cytokine production. Interleukin-1 receptor antagonist (IL-1ra) gene polymorphism has been found to affect disease susceptibility and activity in several inflammatory diseases. In the present study, we analyzed polymorphism of the variable number tandem repeat (VNTR) of IL-1ra in patients diagnosed as having IgAN (n = 106) and normal controls (n = 74). The allele frequency of IL-1ra polymorphism in IgAN patients was not statistically different from that of the control group. There was no significant difference in the carriage rate of the two-repeat allele (IL1RN*2) between IgAN patients and the control group (8.5 vs. 6.8%). The carriage rate of IL1RN*2 was significantly higher in IgAN patients with severe proteinuria (≧1.6 g/day) or increased serum creatinine level (≧2.0 mg/dl; p < 0.05). Furthermore, the carriage rate of IL1RN*2 was significantly higher in patients with severe mesangial cell proliferation (p < 0.01). Our results suggest that IL-1ra polymorphisms are not associated with the development of IgAN in Japanese patients but the presence of IL1RN*2 may be associated with increased disease activity.