Objective A SNP analysis of Japanese type 2 diabetes patients revealed that SNP in the Kcnq1 gene on chromosome 11 was a significant risk factor. The Kcnq1 gene is known as an imprinting gene, and non-coding RNA Kcnq1ot1 expressed from the Kcnq1 gene region controls the expression of neighboring genes via epigenetic modification. However, the association of Kcnq1 mutation with the development of type 2 diabetes mellitus has not been shown yet. We analyzed the effect of the Kcnq1 mutation on the pancreatic β -cells to clarify the development mechanism of type 2 diabetes mellitus. Methods To analyze the effect of imprinting, Kcnq1 heterozygous mice were classified into 3 groups: wild-type mice group (WT); mice with mutations in the alleles inherited from one’s mother (MH); and mice with mutations in the alleles inherited from one’s father (PH). Results An analysis of unclassified Kcnq1 heterozygous mice showed that the mutation had no significant effect on pancreatic β-cell function and glucose tolerance. However, the pancreatic β-cell mass of only the PH decreased significantly. Further, the expression level of Kcnq1ot1 was significantly decreased and the expression level of Cdkn1c was significantly increased in the islets of PH. The ChIP assay revealed that there was a significant decrease in H3K27 methylation in the PH. Conclusion The results showed that the expression level of Kcnq1ot1 located in the Kcnq1 gene region and the expression level of Cdkn1c, a gene adjacent to Kcnq1ot1, were strongly associated with the control of pancreatic β-cell mass in the development of type 2 diabetes mellitus.