This study was conducted to investigate the effect of Garcinia cambogia extracts on body weight gain and fat accumulation in rats rendered obese by a high fat diet. Results showed that Garcinia Cambogia extracts could significantly reduce body weight gain, Lee's index, BMI, the relative weight of epididymal fat, serum glucose, serum triglycerol, serum non-esterified fatty acid and hepatic triglycerol content in rats under high-fat diet, and hepatic lipase activity also was significantly increased in HFD+L group. Adipose triacylglyceride lipase mRNA expression level was significantly increased in the HFD+M and HFD+H groups, hepatic adenosine 5′-monophosphate-activated protein kinase (AMPK) α1 mRNA expression level in HFD+H group was significantly increased, adiponectin mRNA expression level in HFD+L group rats was increased, and adiponectin receptor 1 mRNA expression level was significantly increased in all Garcinia Cambogia extracts treated groups. These results demonstrated that Garcinia Cambogia extracts could attenuated fat accumulation and body weight gain in rat model with high-fat diet induced obesity possibly through regulation of lipolysis gene expression by affecting Adiponectin-AMPK signaling pathway.