p53-induced ring-H2 protein (PIRH2), a newly identified E3 ubiquitin ligase, has been reported to be interacted with p27Kip1 and promote ubiquitination of p27Kip1 independently of p53. p27kip1, a member of the Cip/Kip family of cyclin-dependent kinases inhibitors (CKIs), was shown to control cell cycle progression and promote cell proliferation. While the distribution and function of PIRH2 and p27kip1 in nervous system lesion and regeneration remains unclear. Here, we performed a sciatic nerve injury model in adult rats and studied the dynamic changes of PIRH2 and p27kip1 expression by western blot and RT-PCR in injured rat sciatic nerve. Sciatic nerve crush resulted in a significant up-regulation of PIRH2 and a down-regulation of p27kip1. Besides, we observed that they were expressed widely in both Schwann cells and axons in adult rat sciatic nerve by double immunofluorescence staining. Results obtained by coimmunoprecipitation and double labeling further showed their interaction in the regenerating process. Thus, these results indicate that PIRH2 and p27kip1 likely play an important role in peripheral nerve injury and regeneration.