Diabetes mellitus (DM) is a complex disease caused by absolute or relative insulin deficiency. The C57BLKsJ-db/db mouse model is a useful animal model for studying type 2 DM (T2DM). The present study investigated the association between an antizyme inhibitor 1 (AZIN1) gene polymorphism (rs1062048) and T2DM susceptibility in 2,270 Taiwanese individuals (570 patients with T2DM and 1,700 controls). Additionally, the present study investigated AZIN1 gene and protein expression in the liver tissues of mice in three age groups (4, 16 and 32 weeks) through reverse transcription-quantitative PCR, western blotting and immunohistochemistry. The data indicated that the genotype frequency distribution of the rs1062048 single-nucleotide polymorphism differed significantly between the patients with T2DM and controls (P<0.05). Furthermore, gene and protein expression levels of AZIN1 were significantly lower in early stage and late stage T2DM mouse liver samples than in control samples. Overall, the data suggested that AZIN1 expression is involved in T2DM development.