Context:Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship. Objective:To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents. Design:Cross-sectional secondary analysis of baseline data from a previous randomized trial. Setting:University research facility. Participants:A total of 240 adolescents (68% female), aged 7 to 15 years. Main Outcome Measures:Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance. Results:Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, -5.893 to -0.956) and waist circumference (95% CI, -15.473 to -2.124) showed a negative relationship with LS BMC via HOMA-IR. Conclusions:These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.