Abstract: Peripheral arterial disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces patient’s functional capacity and life quality. Despite relatively effective available treatments, PAD is a serious public health issue associated with a signifcant morbidity and mortality. Ischemia-reperfusion cycles occurring during PAD are responsible for insuffcient oxygen supply, mitochondriopathy, free radical production, infammation and lead to events that contribute to myocyte death and remote organ failures. However, the pathophysiological changes that occur during the ischemic period and at the moment of reperfusion have been poorly reviewed in skeletal muscle fbers. Thus, we will discuss the physiopathology of ischemia and reperfusion from a mitochondrial and cellular levels. A better chronological understanding of the events underlying ischemia-reperfusion will allow us to identify key factors in the development of this pathology and provide new suitable therapies.