This study assessed the effect of chromium (Cr) supplementation on insulin sensitivity and body composition in subjects at high risk for Type 2 diabetes because of family history and obesity. Twenty-nine subjects (14 men, 15 women) were evaluated in a double-blind, randomized, placebo-controlled trial using chromium picolinate (CrPic) (1,000 g/day), or placebo for 8 months of study. Clinical and metabolic evaluations consisted of insulin sensitivity (S I ) and glucose effectiveness (S g ); measurement of glucose tolerance and insulin response to an oral glucose tolerance test (75 g OGTT); and 24-hour glucose and insulin profiles. Anthropometric measures and magnetic resonance imaging (MRI) assessed abdominal fat distribution. Fasting plasma glucose and insulin levels and measures of glycemia (glycated hemoglobin and fructosamine) were also assessed. The CrPic group showed a significant increase in insulin sensitivity at midpoint (P < .05) and end of study (P < .005) compared with controls, which had no significant changes. No change in S g was seen in either group. There was no effect of CrPic on body weight, abdominal fat distribution, or body mass index. However, CrPic significantly improved insulin sensitivity in these obese subjects with a family history of Type 2 diabetes. Improvement in insulin sensitivity without a change in body fat distribution suggests that Cr may alter insulin sensitivity independent of a change in weight or body fat percentage, thereby implying a direct effect on muscle insulin action. Definitive double-blinded, placebo-controlled trials are currently being conducted to confirm this observation in Type 2 diabetic subjects and evaluate the effects of Cr supplementation on insulin action and glycemic control.