Exogenously induced hyperinsulinemia can increase in vivo triglyceride production in rats receiving dietary fructose, either as monosaccharide or as sucrose, but not in those receiving only glucose. Thus, in the presence of fructose, but not glucose, insulin stimulates triglyceride production. Dietary fructose can also impair the removal of circulating triglyceride. Exogenous insulin overcomes this fructose-associated impairment of triglyceride removal. On the other hand, streptozotocin-diabetic rats showed a suppressed triglyceride secretion rate (TgSR) but their plasma triglyceride level was unchanged. Therefore, insulin deficiency may result in not only decreased production of triglyceride but also impaired triglyceride removal from the circulation. Fructose-fed diabetic rats showed higher plasma triglyceride levels than chow-fed diabetic rats without a concomitant increase in TgSR, suggesting impaired triglyceride removal from the circulation induced by fructose in diabetic rats. Glucose-fed diabetic rats did not differ in TgSR or plasma triglyceride level from chow-fed diabetic rats. These observations indicate that circulating insulin and dietary fructose, but not glucose, have a key role in very-low-density lipoprotein triglyceride turnover in rats.