BackgroundWe aimed to evaluate the prevalence and risk factors of depression in type 2 diabetes mellitus with lower extremity arterial disease. Methods: Four hundred and forty-one patients with type 2 diabetes mellitus were recruited from Peking University of International Hospital. All patients completed the Self-rating Depression Scale, which includes 20 items, using a 4-point scale. Univariable and multivariable logistic regression was conducted to investigate risk factors of depression in patients with lower extremity arterial disease. Results: The prevalence of depression in lower extremity arterial disease group was significantly higher than that in non- lower extremity arterial disease group(25% vs 16%, P = 0.018). In lower extremity arterial disease group(n = 215), depression score(46.18 ± 7.38 vs 44.03 ± 6.53, P = 0.003) significantly increased compared with non lower extremity arterial disease group(n = 226). Compared with male depressive patients, the proportion of female depressive patients(38% vs 15%, P = 0.003) was significantly higher in lower extremity arterial disease group. The depression score of female depressive patients(57.83 ± 3.29 vs 55.26 ± 1.59, P = 0.003) was significantly higher than that of male depressive patients. An increased risk of depression in female patients(crude OR: 2.50, 95% CI: 1.38–4.54, P = 0.003; adjusted OR: 2.34, 95% CI: 1.26–4.36, P = 0.008) and in patients with low body mass index(crude OR: 0.88, 95% CI: 0.80–0.96, P = 0.005; adjusted OR: 0.89, 95% CI: 0.81–0.97, P = 0.011) was detected. Conclusion: Both low body mass index and female are risk factors for depression.