Objective: To monitor the physiological characteristics and genes expression of obesity rat model after rambutan peel extract (RPE) treatment. Methods: Twenty-four 12-week-old male rats were divided into 4 groups: normal, obesity, obesity treated with ellagic acid (O-EA) and obesity treated with RPE30 (O-RPE30). Physiological characteristics were monitored by measuring body weight, calorie intake, size of adipocyte and level of triglyceride. Peroxisome proliferator activated receptor gamma (PPARγ), CCAAT/enhancer-binding proteins α and fatty acid binding protein 4 (FABP4) expression were observed using immunohistochemistry, Western blotting and quantitative RT-PCR methods. Results: Body weight gain of O-EA and O-RPE30 rats were lower than obesity group and size of adipocyte cells were smaller than obesity group (P < 0.05), but when we compared to normal group, those groups had higher body weight gain and larger adipocyte cells. The level of triglycerides, protein expression of PPARγ and mRNA level of FABP4 genes were significantly downregulated on O-EA and O-RPE30 compared to obesity group (P < 0.05). Our results indicated that RPE had potential substance as inhibitor of body weight gain, declining of size of adipocyte, level of triglycerides, PPARγ expression and mRNA level of FABP4 gene on obesity rat model. Conclusions: RPE have anti-obesity activity by inhibiting body weight gain, declining size of adipocyte, decreasing triglyceride, PPARγ expression and mRNA level of FABP4 gene on obesity rat model.