Several topics in gene therapy of diabetes mellitus are described as follows: 1) Insulin-producing plasmid or cell is a plausible target of gene therapy of diaetes mellitus. Development in this research includes construction of single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, and new evaluation of K cells which can be engineered to secrete insulin and represent a viable mode of therapy for diabetes. 2)Immunotherapy of diabetes is now focusing on induction of tolerance to beta cell antigens using target cytokins or monoclonal anti-T-cell antibodies. Some have reached the clinical arena. 3)Very rencently, PDX-1 was found to be an important factor to diabetes. Study on mice got to reveal the therapeutical effect of PDX-1.