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Aim of study:To investigate an innovative prescription of TCM "Jing Dan Yi Min Ji",including the content,proportion of each component,efficient dose,major effects and its mechanism.Material and methods:The activities of recombinant human PTP l b and α-glucosidase were measured by enzymatic methods,respectively.The RINm5f cell model was induced by palmitate.The T2DM KKAy mice,the high-fat-diet-induced IRF mice,and the high-calorie-induced DIO beagle dog were used,respectively.The insulin sensitivity in vivo was evaluated by the values of serum insulin,HOMA-IR insulin sensitivity index of whole body,the glucose infuse rate (GIR) in hyperinsulinemic-euglycemic clamp test,insulin tolerance test (ITT),and glucose tolerance test (GTT),respectively.The insulin responses in live,muscle,and adipose tissue were measured by a fluorescence tracer 2-NBDG in hyperinsulinemic-euglycemic clamp test,respectively.Results:Basing on the main principles of relative TCM,according tothe inhibition on the targets PTPlb and a-glucosidase in vitro and the improvement on insulin resistance,glycolipid metabolism disorders,and obesity in vivo,the quality control of the medicinal materials was investigated;the content of the prescription was confirmed according to the synergistic effects;the proportion of each component was chosen by the orthogonal tests in vitro and by the effects in vivo,respectively.Then,the innovative prescription Jing Dan Yi Min Ji was determined with the content of extractions from herbal medicines Rhodiolacrenulata (monarch drug),Cordycepsmilitaris (ministerial drug),and Rhumpalmatum (adjuvant drug) by the proportion of 20:1:1.Its optimal dose was 200 mg/kg orally in mice.Inpharmacodynamics study,the therapeutic effect on diabetes,hyperlipidemia,non-alcoholic fatty liver,and obesity were showed in several animal models,such as KKAy mice,IRF mice,and DIO beagle dog;the mechanism including insulin sensitizing,pancreatic islets protecting was demonstrated;and the inhibition on the molecular targets PTPlb and a-glucosidase was illustrated,respectively.Conclusions:The innovative formula of TCM "Jing Dan Yi Min Ji" can be used for the treatment of T2DM and its complications,and itsmolecular targetsare PTPlb and a-glucosidase.