Nesfatin-1, recently identified as a satiety regulator, elicits an anti-atherosclerosis effect. Our study was designed to determine whether there is an association between serum nesfatin-1 and the development and severity of peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM).This cross-sectional study included 355 T2DM patients (200 without PAD and 155 with PAD).T2DM patients with PAD exhibited marked lower serum nesfatin-1 concentrations than those without PAD. Multivariable logistic regression analysis indicated an inverse association of serum nesfatin-1 concentrations with the development of PAD in T2DM patients (OR 0.008, 95% CI 0.002 to 0.028; P<0.001). Simple linear regression analysis showed a marked correlation between serum nesfatin-1 concentrations and body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein (CRP), and ankle-brachial index (ABI) in T2DM patients. By contrast, multivariable analysis showed only BMI and ABI as independent correlates of serum nesfatin-1.Our study shows an association of serum nesfatin-1 concentrations and the development and severity of PAD in T2DM patients.