The main goal of this investigation is to show how to create and repair different types of median nerve (MN) lesions in the rat. Moreover, different methods of simulating postoperative physiotherapy are presented. Multiple standardized strategies are used to assess motor and sensory recovery using an MN model of peripheral nerve lesion and repair, thus permitting easy comparison of the results. Several options are included for providing a postoperative physiotherapy-like environment to rats that have undergone MN injuries. Finally, the paper provides a method to evaluate the recovery of the MN using several noninvasive tests (i.e., grasping test, pin prick test, ladder rung walking test, rope climbing test, and walking track analysis), and physiological measurements (infrared thermography, electroneuromyography, flexion strength evaluation, and flexor carpi radialis muscle weight determination). Hence, this model seems particularly appropriate to replicate a clinical scenario, facilitating extrapolation of results to the human species. Although the sciatic nerve is the most studied nerve in peripheral nerve research, analysis of the rat MN presents various advantages. For example, there is a reduced incidence of joint contractures and automutilation of the affected limb in MN lesion studies. Furthermore, the MN is not covered by muscle masses, making its dissection easier than that of the sciatic nerve. In addition, MN recovery is observed sooner, because the MN is shorter than the sciatic nerve. Also, the MN has a parallel path to the ulnar nerve in the arm. Hence, the ulnar nerve can be easily used as the nerve graft for repairing MN injuries. Finally, the MN in rats is located in the forelimb, akin to the human upper limb; in humans, the upper limb is the site of most peripheral nerve lesions. Video Link The video component of this article can be found at https://www.jove.com/video/59767/ Introduction Peripheral nerve lesions occur regularly as a result of trauma, infection, vasculitis, autoimmunity, malignancy, and/or radiotherapy 1,2. Unfortunately, peripheral nerve repair continues to present clinically unpredictable and frequently disappointing results 3,4. There is widespread consensus that considerable basic and translational research is still needed to improve the prospect of those affected 4,5,6,7. The rat MN shows great similarities to that of humans 8,9 (Figure 1). Originating from the brachial plexus in the axillary region, this nerve descends into the medial aspect of the arm, reaching the elbow, and branching off to the majority of the muscles in the ventral compartment of the forearm. The MN reaches the hand, where it innervates the thenar muscles and the first two lumbrical muscles as well as to part of the rat's hand skin 9 (Figure 1). Using the rat MN, it is possible to adequately replicate peripheral nerve lesions in humans 10,11,12. This nerve has several potential research advantages relative to the customarily used sciatic nerve. Because the MN is located in the forelimb of rats (akin to t...