Skp2 (S-phase-associated kinase protein-2) is involved in ubiquitination and proteasome-mediated degradation of p27kip1, which plays important roles in cell cycle regulation and neurogenesis in the developing central nervous system (CNS). But their distribution and function in the nervous system lesion and regeneration remains unclear. In this study, we examined expression and relationship of p27kip1 and Skp2 in adult rat spinal cord following sciatic nerve injury. It was illustrated that they localized mainly in neurons and astrocytes of spinal cord, and might also expressed in other glial cells according to the results of immunohistochemistry. Sciatic nerve crush and transection resulted in a significant up-regulation of Skp2 and a down-regulation of p27kip1 in spinal cord. Statistical analysis indicated negative correlation between the number of p27kip1 and Skp2 positive cells in the ventral horn following the sciatic nerve lesion. Immunoprecipitation further showed that they interacted with each other in the regenerating process. Thus, p27kip1 and Skp2 likely play an important role in spinal cord regeneration after peripheral nerve injury.