Background: The high incidence and damage of PAD in people with diabetes has aroused wide attention. We aimed to examine effects of percutaneous lower-extremity arterial interventions (PLEAIs) on endothelial function and inflammation response in type 2 diabetes (T2D) patients with lower-extremity peripheral arterial disease (PAD). Methods: 78 T2D inpatients with PAD were selected into the treatment group. Their venous levels of von Willebrand Factor (vWF) and high sensitivity C reactive protein (hsCRP) were measured. Blood samples were collected from the arterial sheath for vWF and hsCRP tests. Venous levels of vWF and hsCRP were monitored at 24 hours, 48 hours, 1 week, and 2 weeks post PLEAIs. Results: Prior to PLEAIs, venous levels of vWF and hsCRP in the treatment group were significantly higher than the control group. The arterial levels of vWF and hsCRP were 117.9%+/- 15.1% and 5.19 +/- 0.76 mg/L in the control group, while those levels in the treatment group before intervention were also significantly higher than in the control group. In the treatment group prior to inventions, vWF and hsCRP levels of arterial ischemic regions were significantly higher than the non-ischemic regions. The vWF level of arterial ischemic regions after treatment was significantly higher than that prior to treatment. Conclusions: PLEAIs applied to those patients may lead to worse endothelial dysfunction and activated inflammatory response during treatment and 1 week after treatment, which indicates an emerging necessary of early protection or care on endothelial function and inflammatory reaction during and post PLEAIs.