Because approximately 80% of individuals with type 2 diabetes are obese, we examined weight-related QOL in obese persons with diabetes using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Study participants were enrolled in a clinical trial for an obesity medication or a clinical study of gastric bypass surgery. Psychometric properties of the IWQOL-Lite were evaluated separately for obese persons with (n = 225) and without (n = 972) type 2 diabetes. Internal consistency reliabilities were similar for persons with and without diabetes (0.981 versus 0.980). Correlations between IWQOL-Lite scores and body mass index were significant and comparable for persons with and without diabetes. The IWQOL-Lite factor structure was similar for both the diabetic and non-diabetic subjects and consistent with earlier studies. There was no difference between diabetic and non-diabetic subjects on weight-related QOL as measured by the IWQOL-Lite; however, subjects in this study had more impaired weight-related QOL relative to a reference sample of overweight/obese community persons. We recommend the use of weight-related QOL measures in addition to generic and diabetes-specific measures when assessing quality of life in type 2 diabetes, particularly when patients are overweight or obese.