Base on the improvement of compound FF16, compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum, on both insulin resistance and obesity, its effects on type 2 diabetes (T2DM ) was investigated here. The results showed that the levels of fasting and no-fasting blood glucose were controlled in the spontaneous type 2 diabetes KKAy mice; the impaired glucose tolerance (IGT)was improved by decreasing significantly the values of the glucose peaks and the area under the blood glucose-time curve (AUC ) after glucose-loading in glucose tolerance test (OGTT) in both high-fat-diet-induced pre-diabetes IRF mice and KKAy mice, respectively. The pancreatic histopathological analysis showed that the increased islet amount, the enlarged islet area, and the lipid accumulation in the pancreas were reversed by FF16 treatment in both IRF mice and KKAy mice. In the palmitate-induced RINm5f cell model, FF16 could effectively reduce the apoptosis and enhance the glucose-stimulated insulin secretion, respectively. In conclusion, FF16 could improve the T2DM by protecting the pancreatic beta-cells.