OBJECTIVE: Depression is a recurrent and chronic disorder among elderly patients with chronic medical conditions. The objective of this study was to determine predictors of depressive symptomatology in elderly population with type 2 diabetes mellitus. METHODS: A cross sectional study was conducted by administering a health status assessment questionnaire to nearly 1000 older adults (≥65 years) with type 2 diabetes mellitus in the southern United States (Response rate: approximately 85%). The instrument collected information related to demographics, general health status, clinical conditions, medication use, lifestyle, functional status and prior health care service utilization. The Short Form Center for Epidemiologic Studies Depression scale was used to assess depressive symptoms. Partial correlations and multivariate logistic regression analyses were conducted using the linked survey and health care claims data. RESULTS: Of the 885 respondents, about 17% had depressive symptoms. Most participants (60%) were women with mean age of 71 (±8.7) years. Almost 96.7% of patients were using 1 or more antidiabetic medications. Overall, higher general health status was associated with lower level of depression (OR: 0.38, 95%CI: 0.23-0.61). However, impairments in daily activities were associated with higher depression (OR: 1.25, 95%CI: 1.08-1.44). When categorized by type of antidiabetic therapy based on actual prescription claims data, we found that increased number of prescriptions was associated with higher risk of depressive symptoms (OR: 2.39, 95%CI: 1.05-5.44) in patients on insulin compared to those other therapies. In addition, higher risk of depressive symptoms was associated with self reported number of falls (OR: 2.17, 95%CI: 1.1-4.28), and emergency room visits (OR: 1.57, 95%CI: 1.11-2.22) in the previous year in patients on sulphonyl ureas. CONCLUSION: General health status and impairments in daily activities were predictors of depressive symptomatology in elderly with diabetes. Determinants of depression varied according to pharmacotherapeutic class of antidiabetic medications.