Background & Objective: Today, obesity is one of the most important health problems in the world. The purpose of this study was to determine the effects of caffeine and high fat diet on expression of PGC1-α, Fndc-5 and UCP-1 genes in male Wistar rats. Materials & Methods: To study the aim of this survey, 40 male Wistar rats were divided into four equal groups (n=10 in each group), including: 1) control, 2) high fat diet (HFD), 3) caffeine and 4) high fat diet and caffeine (HFD+caffeine) groups. Oral gavage of caffeine was performed in a dose of 6 mg/kg body weight. PGC1-α and Fndc-5 mRNA of muscles, and UCP-1 mRNA of subcutaneous fatty tissue were measured using real-time polymerase chain reaction (qPCR). One-way ANOVA test was used to analyze the data. Results: The results of the present study showed that caffeine prevented overweight and increased PGC1-α, Fndc-5 and UCP-1 gene expression in the caffeine group. There were no significant differences in target genes expression, between the HFD+caffeine and the control group. Conclusion: Based on our results, caffeine is a preventive factor for obesity. It can increase the converting process of white adipose tissue to the brown.