OBJECTIVE: The aim of this work was to find obesity control method without rebound. In our previous studies, gymnemate extracted from Gymnema sylvestre, inhibited oleic acid absorption. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a genetic multifactor syndrome model, exhibits progressive overweight, hyperlipidemia and hyperglycemia. The effect of gymnemate on obesity in OLETF was investigated. METHODS: Three groups were divided (n=4-8): (1) OLETF-gymnemate, gymnema water extract (containing gymnemate) diet (62.5 g/kg) and water (2.5 g/kg) were supplied 2 weeks from 26-28 weeks, following it general diet and water were fed 3 weeks to observe if it rebound, (2) OLETF-control and (3) the counterpart Long-Evans Tokushima Otsuka rats as normal-control. RESULTS: With gymnemate treatment, the food and water intake were decreased about 1/3 and 2/3, along with body weight reduced 57.2+/- 6.4 and 75.5+/- 6.3 g during 1 and 2 weeks respectively. In the end of experiment (3 weeks after gymnemate withdrawal), the body weight was decreased to no significant difference with normal-control. The total cholesterol was decreased about 1/3, moreover LDL+VLDL (low-density and very-low-density lipoprotein) cholesterol decreased about 1/2. The proportion of HDL (high-density lipoprotein) cholesterol to the total cholesterol was increased. The serum triglyceride was decreased to the 1/4 of OLETF control. The level of serum cholesterol and triglyceride was no significant difference in gymnemate group with normal group. CONCLUSION: Supplementation with gymnemate promoted weight loss by its ability to reduce hyperlipidemia, which was no withdrawal rebound: an important discovery. Supplementation with gymnemate is a novel therapeutic tool for weight management, especially in multifactor syndrome.