The main action of SU in the treatment of diabetes mellitus is the stimulation of insulin secretion, and the extrapancreatic action including stimulation of insulin actions in glycogen synthesis and inhibition of glucose production in liver is also reported. The indication of SU in the treatment of diabetes mellitus is for NIDDM usually after diet therapy or suitable exercise therapy. In IDDM and several special cases including diabetic ketoacidosis, severe infection, pregnancy, poor-controlled NIDDM, gangrane, surgery operation, severe renal or hepatic failure et al. insulin therapy should be started. In mild NIDDM, gliclazide, tolbutamide or acetohexamide is used, and in more severe NIDDM glibenclamide is used. The action time of chlorpropamide is very long, usually from 20 to 60 hours, therefore special care should be taken for hypoglycemia. As the causes for secondary failure, transition from NIDDM to IDDM, failure of diet therapy, glucose toxity and others are considered.