Acute axonal nerve lesions cause a hyperintense signal on T2-weighted (T2-w) magnetic resonance imaging (MRI) at the nerve lesion site and distal to it. The aim of this experimental study was to investigate the spatiotemporal evolution and resolution of MR nerve signal changes following denervation and reinnervation, and to relate these findings to electrophysiology and histology. The proximal sciatic nerve of adult rats was ligated by a tight suture that was removed 1 week later to induce complete axotomy and nerve regeneration upon release. Serial electromyography (EMG) and motor nerve conduction studies were performed parallel to MRI at multiple points of time. Moreover, sciatic nerves were taken for quantitative histological evaluation. Nerve hyperintensity on T2-w MRI was present distal to the lesion at thigh level 24 h after denervation preceding the occurrence of spontaneous activity on EMG by 24 h. After 48 h, the entire sciatic nerve and its branches showed an increased signal down to the level of the lower leg. The increased nerve signal regressed with a proximo-distal gradient beginning from week 2 after onset of nerve regeneration in the thigh. On EMG, the first reinnervation potentials were detected at that time at the respective level. Compound muscle action potential (CMAP) in the foot muscle fully recovered 12 weeks after onset of nerve regeneration, that is, 2 weeks after resolution of the hyperintensity along the entire nerve on MRI. Histology revealed axonal degeneration in the acute phase and later nerve oedema parallel to the increased nerve signal on MRI. MR signal alterations occur as early as 24 h after an axonal nerve lesion and correlate with nerve fiber degeneration and later with nerve oedema on histology. MR findings in denervation and reinnervation parallel the electrophysiological changes. Thus, MRI is a promising diagnostic tool for the early detection of acute axonal nerve lesions and monitoring of nerve regeneration.