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Jin-tang-ning(JTN),a Chinese patent medicine,mainly comprised of Bombyx mori L.,has been proved to show a-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2DM).Recently,we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate(MSG)-induced obese mice,suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance(IGT)to T2DM.In this study,we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice.During the 10 weeks of treatment,blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles.The β cell function was quantified using hyperglycemic clamp at the end of the study.JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels,and also ameliorated lipid profile.JTN improved glucose intolerance after 8 weeks of treatment.Meanwhile,JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp.Thus,to investigate the underlying mechanisms of JTN in protecting β cell function,the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones(insulin and glucagon).Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot.Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal a cell distribution.Long-term treatment of JTN recovered islet morphology accompanied by reducing a cell area in KKAy mice.JTN upregulated expression levels of glucokinase(GCK),pyr-uvate carboxylase(PCB)and pancreas duodenum homeobox-1(PDX-1),while down-regulating C/EBP homologous protein(Chop)expression in pancreas of the hyperglycemic clamp,which indicated the improvement of mitochondrial metabolism and relief of endo-plasmic reticulum(ER)stress of β cells after JTN treatment.These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.