We investigated the effect of the herbal extract Uncaria tomentosa (Ut) (50 mg/kg, crude extract, for 5 consecutive days) in two mice models of obesity: high fat diet (DIO) fed mice and the genetic ob/ob mice. Both obese mice exhibited diabetes (151±4 mg*dL-1 vs. 90±2 mg*dL-1 and 205±15 mg/dL vs. 163±11 mg/dL, p<0.05, respectively) and insulin resistance (Kitt: 4.0±0.1%*min-1 vs. 0.5±0.3%*min-1, p<0.05, respectively). The Ut treatment induced a 1.8-fold rise in insulin sensitivity in the DIO mice to similar value to that found in the lean group 5.3±0.5%*min-1 and 20% reduction in the fasting glycaemia of both obese mice. The DIO group had 30% and 50% reduction in the protein expression of IR and IRS-1 protein levels respectively, as compared with the SD group (100%) (p<0.05). The stoichiometric rate of IRS-1 phosphorylation in the 307-serine aminoacyl residue was increased in DIO animals as compared to SD group (145±9% vs. 100±10%, respectively, p<0.05). The Ut treatment reduced the serine phosphorylation of IRS-1 by 25% and by 40%, in the liver of DIO and of ob/ob mice respectively. The Ut treatment improved the inflammatory balance in the liver of both obese animals. There were 20% reduction in the pro-inflammatory index (mRNA IL1b/IL10) associated to 12% reduction in the pro-macrophage activation (mRNA F4/80/Arginase1) in the DIO mice, and even more pronounced reduction in the pro-macrophage activation to 40% in the ob/ob. Results herein reported prompted to the conclusion that the improvement in insulin sensitivity induced by the Uncaria tomentosa crude extract is associated with a reduction in inflammatory index in the liver of obese mice.