Abstract: Objective: To study the effect of the composite granules of bitter melon and mulberry leaf (CGBM) on improving dysfunction of obesity rats induced by high-fat diet. An explorative study was conducted on CGBM for its regulation of lipid-glucose metabolism and intestinal mucosal barrier in high-fat diet-induced obese rats, in order to provide data support for the further development of CGBM. Methods: SD rats were randomly divided into control group, model group, CGBM low-dose and high-dose group. The rats in the control group were given basic diet, whereas the others were fed in the high-fat diet to establish obesity model. The rats in the low-dose (0.5 g/kg) and high-dose (1.0 g/kg) groups were given CGBM by intragastric administration per day for 8 weeks. The rats in other groups were given the same volumes of normal saline by the same method for 8 weeks. The body weight, serum glucose and lipid levels (such as GLU, GSP, TC, TG, HDL-C, LDL-C) of rats were measured. The morphology of liver and colon tissues were observed by HE staining, and the expression of tight junction protein occludin in colon tissues were detected. Results: CGBM could effectively reduce the body weight, and lower the high level of serum glucose and lipid in obese rats. The phenomenon of excessive lipid droplet in liver and the abnormal morphology of glands in colon mucosa were also improved by CGBM. The results also indicated that the CGBM could effectively ameliorate the lower expression level of occludin protein in obesity rats (P<0.05). Conclusion: CGBM has the obvious improvement effect on dysfunction of glucose and lipid metabolism in obesity rats induced by high-fat diet. The hepatic and intestinal injuries caused by high-fat diet were also repaired by CGBM. This study would have an important significance on accelerating the development of CGBM and its mechanism research.