Objective Wallerian degeneration (WD) is still a subject of modern neuroscience.It occurs in peripheral nervous system (PNS) which is a process that nerve fiber is cut or crushed.It is also known as anterograde degeneration, or orthograde degeneration, or secondary degeneration.During WD, the distal axons begins degeneration and macrophages enter the distal axons area to remove the myelin and axonal debris of PNS.Immune cells, accompanied by Schwann cells clear the debris from the degeneration.Regeneration is rapid and supported by Schwann cells through growth factors release of a lesion follows degeneration in PNS.A large number of genes are differentially regulated during the stages of WD in the development and pathology of WD in the peripheral nerve injury initiating these responses has remained largely elusive.Methods In this study, we analyzed gene expression patterns of short-term (0, 0.5, 1, 6, 12, 24 h) and long-term (0, 1, 4, 7, 14, 21, 28 d) series carrying the WD of the distal nerve stump after rat sciatic nerve injury using gene chip microarrays.Screening of differential genes; analysis of gene expression trends; Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and signal-flow analysis; real-time PCR, Western blot and immunohistochemistry.Results GO classification indicated enrichment in genes related to cell adhesion, extracellular matrix, microglial cell activation, positive regulation of synaptic plasticity, positive regulation of chemokine production, positive regulation of acute inflammatory response, nerve development and positive regulation of neuron differentiation, neurogenesis.KEGG pathway analysis showed high expression of genes relating to T cell receptor signaling pathway, Jak-STAT signaling pathway, apoptosis, cytokine-cytokine receptor interaction, toll-like receptor signaling pathway and p53 signaling pathway.The data were validated with real-time PCR, Western blot, and immunohistochemistry.Conclusion These results will help to much better understand how the tendency of gene expressions, gene ontology, signaling pathway, signal-flow of WD.The study provides a global view of gene expression profiles of rat sciatic nerve injury in WD, contribute to future investigations on the molecular mechanisms of WD regulating nerve degeneration and regeneration and also provide information for the functional analysis of differentially expressed genes in WD.