Abstract: The purpose of this study was to investigate the hypoglycemic effect and the safety of medicinal formula composed of Cyclocarya paliurus and Mulberry leaves. An experimental diabetic rat model was established by high energy diet plus small dosage of auoxan(ALX). At the same time, each group rats were given distilled water(blank and model), metformin(Met), Cyclocarya paliurus aqueous extract(CP), Mulberry leaves aqueous extract(ML)and the different proportions of aqueous extract mixtures of Cyclocarya paliurus and Mulberry leaves(CM1, CM2 and CM3), respectively. Fasting blood glucose(FBG), OGTT, TC, TG, LDL-C, HDL-C, insulin and liver and kidney function related index were gauged to evaluate the hypoglycemic effect and the safety of samples. The results showed that FBG level of the rats in CM1, CM2 and CM3 groups decreased 21. 64%, 16% and 12. 55%, respectively, comparing with that of model group. Moreover, FBG, glucose tolerance and pancreatic tissue morphology were remarkably improved in CM1 group. TC and LDL-C levels of rats in ML and CM3 groups decreased significantly compared with the those of Model group(P< 0. 05), which showed ML and CM3 were beneficial to regulate the blood lipid level in diabetic rats. Furthermore, all the administration groups had no adverse effect on liver function index. The down regulation of kidney function index of CP, ML, CM1, CM2 and CM3 groups comparing with model group indicated that Cyclocarya paliurus and Mulberry leaves could alleviate the injury of liver and kidney. Our results demonstrated that the medicinal formula composed of Cyclocarya paliurus and Mulberry leaves were favorable to reduce blood glucose and can regulate lipid metabolism without liver and kidney toxicity.