Abstract: Diabetes mellitus and its complications become serious threat to human health. Due to the ambiguous mechanism of diabetes pathogenesis, the development and promotion of anti-diabetes drugs have greatly hindered. Clinical and animal experimental results suggest a close association between 5-hydroxytryptamine(5-HT) and the occurrence and development of diabetes. With the deepening of research, the peripheral 5-HT system has shown its potential as an important target for curing diabetes. First of all, peripheral 5-HT in the occurrence and development of diabetes and its complications is described, and then the mechanism of 5-HT regulating diabetes is discussed, then 5-HT receptors which associated with diabetes complications are systematically summarized, finally, the prospect of how to use drugs to prevent and cure diabetes through 5-HT system is put forward.