AIM:To study the relationship of lmp2 and DR3 genes with type I diabetes mellitus.METHODS:lmp2 genotypes and DR3 were identified in 68 patients with type I diabetes mellitus (I -DM) and 71 healthy controls. Then,I -DM patients and controls were respectively allocated into DR3-positive and DR3-negative groups. The frequencies of lmp2 and DR3 gene in random subjects, and lmp2 genotypes in DR3 matched subjects were compared between I -DM patients and controls. At the same time, I DM patients were divided into 3 groups based on the onset age of diabetics:group A < = 14 years, group B 15-30 years and group C > = 31 years.RESULTS:The frequency of DR3 in I-DM patients was significantly higher than that in controls (47% vs 21%, P < 0.005), and it was significantly higher in group A than that in group B+C (70% vs 36%, X(2) = 7.07, P < 0.01). There was a significant difference among groups with different onset age of diabetics (X(2) = 8.19, rp = 0.33, P <0.05). In random subjects, the frequency of lmp2-R/R in I -DM patients was lower (43% vs 61%, P <0.05)and lmp2-R/H higher (53% vs 28%, P<0.05) than that in controls, and there was no significant difference among groups with different onset age of diabetics.In DR3-positive subjects, the frequency of lmp2-R/R in I-DM patients was lower (47% vs 87%, P<0.05) and lmp2-R/H higher (47% vs 13%, P <0.05) than that in controls. In DR3-negative subjects,the frequency of lmp2-R/H in I -DM patients was higher than that in controls (58% vs 32%, P <0.01), but the frequency of lmp2-R/R and lmp2-H/H was not significantly different between these two groups.CONCLUSION:DR3 gene may be one of the susceptible genes of I-DM,and significantly related to the onset age of diabetics, and the persons with DR3 may have an younger onset age of diabetes.The lmp2-R/R may be the protective genotype of I-DM, and lmp2-R/H the susceptible genotype. These were not affected by DR3 gene. lmp2 genotypes were not related with the onset age of diabetics.