In order to explore the anti-obesity mechanism of Pu-erh tea, the effect of MC4R expression mediating the anti-obesity activity of Pu-erh tea extracts in high-fat diet-induced obesity in rats was observed. SD rats were divided into three groups: normal diet control group (ND group), high-fat diet group (HF group) and high-fat diet with Pu-erh tea extracts group (PTE group). Body weight and serum lipids were measured, and fat mass were observed. Expressions of MC4R in epididymal fat tissues of rats were measured by RT-PCR and Western blot. Pu-erh tea extracts prevented the increases of body weight and fat tissues induced by high-fat diet, and it reduced the blood lipids. MC4R mRNA and protein levels were markedly increased in adipose tissue of rats fed with high fat diet for intervention with Pu-erh tea extracts. Pu-erh tea could reduce diet-induced body weights and decrease blood lipids, its mechanism might be related to the regulation of obesity gene MC4R.