Chemotherapy-induced peripheral neuropathic pain is a major dose-limiting and therapy-limiting adverse effect that is particularly difficult to treat. Puerarin, a major active ingredient of traditional Chinese plant medicine Gegen, is commonly used in the treatment of myocardial and cerebral ischemia. However, the effects of puerarin on neuropathic pain are still unknown. Therefore, the aim of this study is to examine the effects of puerarin on neuropathic pain. In this study, the effects of puerarin were tested in-vivo on a rat model of paclitaxel-induced peripheral neuropathic pain (PIPNP). The results show that a single injection of puerarin produced short-term analgesic effect on pre-established PIPNP, as indicated by decreased mechanical allodynia and thermal hyperalgesia in comparison with paclitaxel-treated rats. Repeated doses of puerarin, given during PIPNP induction, prevented the development of PIPNP. This prophylactic effect of puerarin was associated with suppressed paclitaxel-induced transient receptor potential vanilloid 1, calcitonin gene-related peptide and substance P up-regulation in the dorsal root ganglia. These findings revealed the therapeutic potential of puerarin in treating and preventing chemotherapy-induced peripheral neuropathic pain.