Although the neuropathology of ischaemic fibre degeneration is relatively well known, its pathogenesis is poorly understood. One of the presumed mechanisms is oxidative stress, causing the breakdown of the blood-nerve barrier (BNB) and ending in lipid peroxidation. We evaluated the effect of ischaemia and reperfusion on the sciatic-tibial nerve of the rat and investigated the biochemical, pathological, and functional evidence of BNB disruption and lipid peroxidation. The distal portion and trifurcation of the sciatic nerve were rendered ischaemic by clamping the femoral vessels for 3 h and followed by varying durations of reperfusion. Reperfusion resulted in an increase in lipid peroxidation beginning from the first hour and increasing until the seventh day, followed by a gradual decline over the following weeks. Nerve oedema and ischaemic fibre degeneration (IFD) consistently became more severe and prominent with reperfusion, indicating that oxidative stress damages the BNB and causes IFD. Results of functional testing by the sciatic function index correlated with other parameters as walking track analysis results got worse as reperfusion periods increased. Impairment of walking patterns was more striking after the first day and continued up to the third week. These data indicate that severe ischaemia of the peripheral nerve results in reperfusion injury, functional impairment, and disruption of the BNB. Microvascular events, which may occur during reperfusion, may be important in amplifying the nerve fibre degeneration that initiated during ischaemia.