Obesity results from an imbalance between caloric intake and energy expenditure. Non-shivering thermogenesis in brown adipose tissue (BAT) is primarily linked to maintenance of body temperature, however the observation that BAT is stimulated by consumption of a high fat diet (HFD) in rodent models, a phenomenon referred to as diet-induced thermogenesis, suggests that BAT activation can be a mechanism of protection against obesity development. Since BAT thermogenesis may be important to whole body energy balance, disruption on diet-induced thermogenesis may lead to obesity. Sub-clinical inflammation is a hallmark of human and experimental obesity. However, no previous study has addressed the connection between BAT thermogenesis and inflammatory pathways. In the present study, we used IL10-/- mice exposed to a HFD in order to investigate the role of this important anti-inflammatory cytokine on diet-induced thermogenesis and its consequences on the development of obesity. Eight week old male IL10-/- and C57BL/6 mice were fed on a HFD (IL10H and CH groups, respectively) or chow (IL10C and CC groups, respectively). All experiments were conducted in accordance with the principles and procedures described by “Guide for the Care and Use of Laboratory Animals”, approved by the University of Campinas Ethical Committee. The results described were confirmed in, at least, two independent experiments. Data was analyzed by ANOVA and Students t Test, as appropriate. After 8 weeks, IL10-/- and C57BL/6 mice fed on chow had similar body mass gain, and when exposed to a HFD both showed higher weight gain than those on chow diet (p<0,05) . However, IL10H mice had a significantly higher weight gain than CH mice (p<0,05). Since no difference on caloric ingestion was detected between IL10-/- and C57BL/6 mice, we assessed O2 consumption/CO2 production by indirect calorimetry. IL10C consumed less oxygen than CC mice (p<0,05) and the HFD ingestion resulted in increased oxygen consumption (VO2) for both animal models (p<0,05) but there was no difference between IL10H and CH. Although statistically the VO2 is not different between the IL10H and CH groups, IL10H mice consumed slightly less oxygen. The impact of these phenomena may be cumulative through the 8 weeks and contribute to differences in body weight. In addition, the expression of UCP1 in BAT (n=6) was significantly lower in IL10-/- mice as compared to C57BL/6 mice on the chow diet (p<0,01). When exposed to the HFD, both animals increased UCP1 levels (p<0,01) , but IL10-/- mice had a lower increase than C57BL/6 ( p<0,05). Thus, in the absence of IL10 there is an impairment of diet-induced thermogenesis leading to increased body mass gain, highlighting the key role of inflammation on energy balance disruption that results in obesity.