The influence of peripheral arterial insufficiency and severe exercise on muscle mass, capillarity and mitochondrial content was analyzed in rat extensor digitorum (EDL) muscles. Animals (n = 4) were assigned to three groups: ligation of the common iliac artery, chronic electrical stimulation (10 Hz, 6 h/day) of the peroneal nerve, and a combination of both. All interventions were carried out unilaterally, animals were treated for 10–12 days. The effects of the experimental procedures were judged by a paired analysis of treated muscles to contralateral untreated muscles of the same animals. Ligation of the common iliac artery alone had no effect on the quantitative structural composition of the EDL muscle. If ischemia was combined with electrical stimulation, a massive reduction in muscle mass occurred. However, as a consequence of an increase in mitochondrial and capillary density, the total mitochondrial volume and the total capillary length was maintained in these muscles. Stimulated ischemic muscles thus had improved conditions for aerobic energy supply for the remaining reduced myofibrillar apparatus. Extensive swelling of capillary endothelial cells was observed in stimulated as well as in contralateral muscles of all animals that received electrical stimulation. It is concluded that severe exercise may lead to extensive damage in ischemic skeletal muscles.