Abstract: Obesity is a problem of public health, mainly because it is associated with many conditions such especially insulin resistance (IR). Currently, several strategies have been used in order to reduce the total body weight, among these there is a growing evidence supporting the use of products of plant origin, including the Ilex paraguariensis, whose common name is yerba mate. Various studies have shown that the compounds found in yerba mate has several biological functions, such as antioxidant, anti-inflammatory, immunomodulatory, anticancer, modification of cholesterol metabolism and others. Although several studies highlight the biological functions of yerba mate, there are lack of evidence providing their ability to modulate expression of genes related to obesity and its effect on the insulin signaling pathway. Thus, the aim of this study was to evaluate the effects of yerba mate in gene expression that regulate adipogenesis and insulin signaling pathway. Our data showed yerba mate (1,0 g/kg) in animals subjected to high fat diet, increased different gene expression responsible for the activation of the AKT, reduction of FOXO1 and NF-kB nuclear translocation, reduction gene expression of PEPCK and G6Pase involved in gluconeogenesis process in liver. The effects of yerba mate in insulin signaling was confirmed by IRS-1, IRS-2 and AKT protein analysis, reduction in insulin test tolerance by KITT and reduction in glucose. Our data also showed in 3T3-L1 cell culture that yerba mate and some of its major bioactive compounds (chlorogenic acid, rutin and quercetin), act in an early stage of adipocyte differentiation and modulate different gene expression that regulate adipogenesis. Additionally, yerba mate can act in vitro and ex vivo in WNT pathway, seen by the increased expression of different genes in this pathway resulting in a significant repression of C/EBP'alfa' and PPARy2, the most important transcription factors essencial for the occurrence of adipocyte differentiation. This findings collaborate to elucidate the reduction of body weight and epididymal fat observed in animals subjected to high fat diet treated with yerba mate for 60 days, which reduces the production of cytokines, particularly TNF-'alfa', contributing partially to the improvement in insulin signaling observed after intervention Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Ribeiro, Marcelo Lima (advisor), Universidade Estadual de Campinas. Instituto de Biologia (institution), Programa de Pós-Graduação em Genética e Biologia Molecular (nameofprogram), Sartorato, Edi Lúcia (committee member), Cintra, Dennys Esper (committee member), Ong, Thomas Prates (committee member), Rogero, Marcelo Macedo (committee member).