In the present study, we examined the preventive effects of metformin on hepatic carcinogen diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb (db/db) mice, which exhibit obesity and diabetes, focusing on improvements in insulin resistance, inhibition of the Akt/mTOR signaling pathway, and amelioration of adipokine imbalance. This evidence concerns the gene INS and diabetes mellitus.