CUG-binding protein 1, a member of the CELF (CUGBP and embryonic lethal abnormal vision-like factor) family of RNA-binding proteins, is shown to be multifunctional, regulating many posttranscriptional processes including alternative splicing, deadenylation, mRNA decay, and translation. Recently, CUGBP1 is found to represses p27 IRES activity and inhibits expression of endogenous p27 in cultured breast cancer cells. However, the roles of CUGBP1 in central nervous system injury remain unknown. In our study, we performed acute spinal cord injury (SCI) model in adult rats in order to research the expression changes of CUGBP1 in spinal cord. Western blot analysis showed a marked upregulation of CUGBP1 after SCI. Immunohistochemistry analysis revealed a wide distribution of CUGBP1 in the spinal cord. Double immunofluorescence staining indicated that CUGBP1 immunoreactivity was increased predominantly in neurons and astrocytes after SCI. Moreover, colocalization of CUGBP1/proliferating cell nuclear antigen (PCNA) was detected in GFAP positive cells. We also examined the expression profiles of p27, which was up-regulated after SCI. To further understand whether CUGBP1 plays a role in astrocyte proliferation, we applied LPS to induce astrocyte proliferation in vitro. Western blot analysis demonstrated that CUGBP1 expression was positively correlated with PCNA expression, and the p27 expression was negatively correlated with CUGBP1 expression following LPS stimulation. Our results suggest that CUGBP1 might be implicated in the pathophysiology of spinal cord after SCI.