This study evaluated the epidemiological relationship between diabetes and incident depression, as well as antidepressant medication utilization among indigent care patients diagnosed with diabetes. Medical data for 2,886 subjects receiving care in a public indigent care provider network were utilized for this study. Diagnoses of diabetes, depression, and other comorbid medical conditions were identified from the electronic medical record. Prescription claims data from the clinic pharmacy network were used to evaluate medication-taking behaviors. Clinical laboratory data were extracted, as available, from the electronic clinic records. After controlling for the influence of age, gender, race/ethnicity, marital status classification, and Charlson score, a diagnosis of diabetes was associated with a 42 percent reduction in odds of new-onset depression (p = 0.021). In the a priori analysis of factors associated with new-onset depression among diabetic patients, none of the risk factors evaluated were associated with incident depression at a statistically significant level. Post-hoc exploratory analyses revealed that female gender and White non-Hispanic race/ethnicity were associated with increased odds of a prevalent diagnosis of depression among diabetic patients. Patients with diabetes were more likely to be prescribed selective serotonin reuptake inhibitors (SSRIs) as their initial antidepressant medication compared to non-SSRIs. Diagnosis of diabetes was not associated with antidepressant switch, discontinuation, or 6-month antidepressant adherence; however, diagnosis of diabetes was associated with a higher level of 12-month antidepressant adherence (p = 0.024). Diagnosis of diabetes was also associated with a higher level of 3-month antidepressant persistence (p = 0.004), but not 12-month persistence. There were no statistically significant relationships observed between initial class of antidepressant medication prescribed and any of the medication-taking behaviors evaluated. For subjects with available data (n = 106), glycemic control was evaluated in terms of hemoglobin A1c. Increased antidepressant medication adherence was associated with higher hemoglobin A1c values during follow-up. Results suggest that prevalent diabetes is associated with a reduced risk of diagnosis of new-onset depression in indigent care patients. Further research is necessary to evaluate the effect that chronic comorbid medical conditions such as diabetes may have on antidepressant medication-taking behaviors, and the relationship between antidepressant exposure and glycemic control. / text