Peripheral arterial disease (PAD) is a growing health problem for many Americans and often occurs along with other cardiovascular risk factors, including diabetes mellitus (DM), low-grade inflammation, hypertension, and lipid disorders. Intermittent claudication (IC), an early manifestation of PAD, commonly leads to reduced quality of life for patients who are limited in their ambulation. While recent wide adoption of percutaneous peripheral interventional (PPI) techniques has increased the number patients being aggressively treated for IC, the overall effectiveness of PPI for the treatment of IC is not well known, especially for DM patients who have both hemodynamic and functional obstacles to treatment success. This review is designed to illustrate how treatment outcomes for IC can be measured by different modalities and how diabetes and inflammation can influence those outcomes. In the setting of greater concern for health care resources and clinical accountability, better understanding of treatment outcomes and efficacy will help us manage these complex challenges.