Objectives To evaluate the effect of a polyphenol-rich berberis microphylla (Calafate, a Chilean native berry) extract in obese mice. Methods 40 8-week old C57BL6 mice were divided (n = 10 each) in 4 treatments for 4 months: Control diet (C; 11% fat), Control diet/Calafate (CC), High fat diet (HF; 58% fat), and High fat diet/Calafate (HFC). Animals received food and water ad libitum. CC and HFC were treated with a daily dose of 50 mg total polyphenols/kg weight of Calafate extract. IPGTT and indirect calorimetry were performed at month 2 and 3 respectively. At month 4, animals were euthanized and final body weight were recorded, and samples of interscapular brown (BAT), epididymal white (eWAT) and inguinal white (iWAT) adipose tissues were obtained. Gene expression of inflammatory markers (MCP-1, TNF-α, Leptina, ADIPOQ and F4/80) on eWAT and thermogenic markers (UCP-1, PGC1α, SIRT1, PRDM16, PPARα/γ, DIO2) on BAT and iWAT were analyzed. 2x2 ANOVA statistical analysis was applied. Results HF presented higher body weight than HFC mice (p < 0.001), from day 40 of treatment. Also, BAT weight was increased (p < 0.05). Basal glycemia was higher in HF than C (p < 0.05), but not than HFC. Energy expenditure was higher in HFC (p < 0.05). Differential expression of MCP-1, leptin and F4/80 on eWAT was detected. In BAT, UCP-1, PGC1α, PPARα and SIRT1 expression were higher in HFC than HF (p < 0.05). In iWAT, expression of PGC1α, PPARα, PRDM16, SIRT1, y DIO2 were also increased (p < 0.05). Conclusions a polyphenol-rich Calafate extract decrease body weight increase, augment BAT mass, modulate inflammation, and promote energy expenditure, which was related to higher expression of thermogenic genes in obese mice. Funding Sources FONDECYT 1171550 (CONICYT, CHILE).