Abstract Topiramate (TPM), a novel anti-convulsant currently approved for the treatment of epileptic disorders, has been shown to possess neuroprotective effects in models of cerebral ischemia, status epilepticus, and facial nerve lesion. Furthermore, pilot studies showed an effect of TPM in neuropathic pain models. Here, we studied the anti-hyperalgesic and neuroprotective efficacy of TPM in rat models of peripheral nerve lesions. Rats with a unilateral chronic constrictive injury (CCI) or a crush lesion of the sciatic nerve were treated with a twice-daily dose of 20 mg/kg of TPM. Behavioral and neurophysiological tests were used to measure pain-related behavior, motor, and sensory function. Morphometry was performed to evaluate sciatic nerves. In CCI, treatment with TPM attenuated mechanical hyperalgesia and cold allodynia. In sciatic nerve crush, TPM reduced cold allodynia and attenuated thermal hyperalgesia at the early and late phase of the observation. There was no difference in the numbers of surviving or regenerating nerve fibers between saline- and TPM-treated rats in either model. Electrophysiological studies carried out over a period of 3 months after sciatic nerve crush did not show major differences between TPM- and saline-treated rats. In conclusion, we could show moderate anti-hyperalgesic effects but could not prove a neuroprotective effect of TPM in these two rat nerve injury models using electrophysiological and morphometric methods.