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Abstract: Aim: We aimed at estimating excess medical expenditures associated with major depressive disorder (MDD) among working-age adults diagnosed with diabetes, disaggregated by treatment mode: insulin-treated diabetes (ITDM) or non-insulin-treated diabetes (NITDM). Methods: We analyzed data for over 500,000 individuals with diagnosed diabetes from the 2008 U.S. MarketScan claims database. We grouped diabetic patients first by treatment mode (ITDM or NITDM), then by MDD status (with or without MDD), and finally by whether those with MDD used antidepressant medication. We estimated annual mean excess outpatient, inpatient, prescription drug, and total expenditures using regression models, controlling for demographics, types of health coverage, and comorbidities. Results: Among persons having ITDM, the estimated annual total mean expenditure for those with no MDD (the comparison group) was $19,625. For those with MDD, the expenditures were $12,406 (63%) larger if using antidepressant medication and $7322 (37%) larger if not using antidepressant medication. Among persons having NITDM, the corresponding estimated expenditure for the comparison group was $10,746, the excess expenditures were $10,432 (97%) larger if using antidepressant medication and $5579 (52%) larger if not using antidepressant medication, respectively. Inpatient excess expenditures were the largest of total excess expenditure for those with ITDM and MDD treated with antidepressant medication; for all others with diabetes and MDD, outpatient expenditures were the largest excess expenditure. Conclusions: Among working-age adults with diabetes, MDD was associated with substantial excess medical expenditures. Implementing the effective interventions demonstrated in clinical trials and treatment guidelines recommended by professional organizations might reduce the economic burden of MDD in this population. [Copyright &y& Elsevier]