Summary Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic b-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and 2, serum glucose concentration and water intake in coffee ingestion (Coffee group) tended to be lowered or was significantly lowered compared to those in water ingestion (Water group) instead of coffee. In Exp. 1, the values for water intake and serum glucose concentration in caffeine ingestion (Caffeine group) were similar to those in the Water group. In Exp. 2, serum glucose concentrations in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those in the Water group. Pancreatic insulin contents tended to be higher in the Coffee and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently, we showed that coffee ingestion also suppressed the deterioration of hyperglycemia in diabetic mice which had been already injected with STZ. This study showed that coffee ingestion prevented the development of STZ-induced diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or decaffeinated coffee ingestion did not significantly suppress STZ-induced hyperglycemia. These results suggest that the combination of caffeine and other components of decaffeinated coffee are needed for the preventive effect on pancreatic b-cell destruction. Coffee ingestion may contribute to the maintenance of pancreatic insulin contents. Key Words streptozotocin, diabetes, hyperglycemia, coffee, caffeine In 2015, 415 million people worldwide were estimated to be affected by type 2 diabetes (1). The International Diabetes Federation estimates that this will rise to 642 million individuals by the year 2040, and warns that the prevalence of type 2 diabetes will increase. These increases are caused by changes in environmental factors such as quantity and quality of food and exercise, and therefore modification of environmental factors can contribute to the prevention of type 2 diabetes.In humans, many studies have revealed an association between coffee consumption and decreased risk of type 2 diabetes. A meta-analysis of 28 studies published between 1966 and 2013 showed that daily consumption of six cups of coffee was associated with a 33% lower risk of diabetes, and that coffee consumption dose-dependently reduced the risk of type 2 diabetes (2). In addition, the reduction in type 2 diabetes risk was observed with both, caffeinated and decaffeinated coffee. However, the mechanism of the anti-diabetic effect of coffee remains unclear.Previously we reported that coffee had an anti-diabetic effect in both spontaneous and diet-induced type 2 diabetes in animal models (3, 4). In KK-A y mice, which spontaneously develop type 2 diabetes, coffee ingestion suppressed hyperglycemia, hyperinsulinemia, hyperlipidemia...