Diabetes mellitus (DM) is a chronic disease. The KK Cg-A/J (KK-A) mouse is an animal model to study type 2 diabetes mellitus (T2D) disease. The present study assessed the expression of hematopoietically expressed homeobox (HHEX) protein in liver tissues of different age groups of mice (6, 16 and 42 weeks) by immunohistochemistry (IHC). The results demonstrated a significant decrease in the percentage of HHEX-positive cells in KK-A mice as compared with that in KK-α/α control mice. Furthermore, in Taiwan's Han Chinese population, genotypic and allelic frequency distributions of the rs61862780 single-nucleotide polymorphism (SNP) in the gene were investigated. The results demonstrated that in the rs61862780 SNP of the 3'-untranslated region (UTR) of HHEX, the frequency of the CC genotype was higher in patients (6.0%) than in controls (2.7%), while the TT genotype frequency was about equal. In the same SNP, the frequency of the C allele was higher in patients (21.0%) than in controls (17.3%), while the T allele frequency was about equal. These results may pave the road for exploring the KK-A mouse model and the HHEX SNP rs61862780, which was correlated with the susceptibility to T2D in a Chinese population. Based on these findings, an association of gene expression with pathological features of T2D was indicated.