Abdominal obesity is a major risk factor for insulin resistance, type 2 diabetes and cardiovascular diseases. Dietary fat induces insulin resistance in humans and rodents. The current study investigates whether a Chlorogenic acid/Chromium III supplement rescues obesity and insulin resistance caused by high-fat feeding of male C57BL/6 J mice for 7 weeks. Administering an oral daily dose of this supplement in the last 3 weeks of feeding reversed diet-induced body weight gain and insulin resistance, assessed by hyperglycemia, glucose intolerance and insulin intolerance. Indirect calorimetry analysis revealed that this effect is mediated at least partly, by increasing energy expenditure and spontaneous locomoter activity. These findings underscore the important role that chlorogenic acid and chromium play in maintaining glucose metabolism and insulin response in mice fed a high-fat diet.