Objectives: To assess whether type 2 diabetes mellitus (DM2) and DM2 complications are associated with presence and severity of depression among Alaska Native and American Indian people (AN/AIs). Design: Retrospective, cross-sectional analysis of medical records. Setting: Southcentral Foundation Primary Care Center (SCF-PCC) in Anchorage, Alaska. Participants: Total of 23,529 AN/AI adults. Primary Outcome Measures: Patient Health Questionnaire (PHQ) scores (0-9 negative, 10-14 mild, 15-19 moderate, 20+ severe) and DSM-IV depression diagnosis. Results: DM2 prevalence was 6% (n=1,526). Of those with DM2, 19% (n=292) had one or more DM2 complications and average HbA1c was 7.1%. Prevalence of depression diagnosis was similar between AN/AIs with and without DM2 (P=.124). Among those screened for depression (n=12,280), there were similar rates of PHQ severity between those without and with DM2; respectively 4% (n=452) vs 4% (n=42) mild, 4% (n=404) vs 3% (n=29) moderate, and 4% (n=354) vs 4% (n=38) severe. In multivariable logistic regression, DM2 was not associated with PHQ severity (OR 1.02, 95% CI 0.81-1.27) or depression diagnosis (OR 1.27, 95% CI 1.00-1.62). Increased odds of depression and higher depression severity were associated with female sex, younger age, being unmarried, substance abuse/dependence, and increased ambulatory visits. Depression was associated with number of other chronic conditions among AN/AIs with DM2 but not with number of complications. Conclusions: Presence and severity of depression among AN/AI primary care patients was not significantly associated with DM2 nor DM2 complications, despite a slightly higher rate of depression diagnosis among those with DM2. (Ethn Dis. 2013;23[1]:56-64)