© 2016 The Obesity Society Objective: To test the hypothesis that an 8-year intensive lifestyle intervention (ILI) suppresses aging-dependent changes in regional lean mass (LM) and fat mass (FM) among people with overweight/obesity and type 2 diabetes. Methods: Regional body composition was measured by dual-energy X-ray absorptiometry within a subset of 1,019 volunteers (45–75 years old) in the Look AHEAD study randomized to ILI or diabetes support and education (DSE). The ILI goal was to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. Results: Over 8 years, the DSE group exhibited a linear loss of LM and FM. During year 1, the ILI group lost LM and FM. Between years 1 and 8, the ILI group regained most FM in all regions; regional LM converged with that of the DSE group; the percent of LM loss was greater for the leg than for the trunk. Among both groups, regional LM and FM change was proportional to the size of the region, trunk > leg > arm. Conclusions: Aging-dependent LM losses, particularly in the leg region, were not suppressed by ILI. The long-term consequences of rapid LM and FM loss and subsequent regain mostly as fat are unknown.