Neopterin is a marker of macrophage activation that has exhibited high plasma levels in atherosclerotic diseases including coronary heart disease and critical limb ischemia. The role of neopterin in chronic peripheral arterial disease (PAD) has yet to be elucidated. In the present study, neopterin (Ν) serum concentrations were analyzed in asymptomatic (AsP) and symptomatic (SyP) patients with PAD as well as controls (C). In total 120 subjects, 40 AsP [ankle brachial index (ABI) ≤0.90], 40 SyP (ABI ≤0.90 plus pain in legs) and 40 controls (ABI >0.9) were enrolled. The results of the present study showed that neopterin plasma levels were statistically different among the groups. These findings demonstrated that activation of N‑mediated monocyte‑macrophage, was also observed in chronic PAD.