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Wallerian degeneration and nerve regeneration after injury are complex processes involving many genes, proteins and cytokines. After different peripheral nerve injuries the regeneration rate can differ. Whether this is caused by differential expression of genes and proteins during Wallerian degeneration remains unclear. The right tibial nerve and the common peroneal nerve of the same rat were exposed and completely cut through and then sutured in the same horizontal plane. On days 1, 7, 14, and 21 after surgery, 1–2 cm of nerve tissue distal to the suture site was dissected out from the tibial and common peroneal nerves. The differences in gene and protein expression during Wallerian degeneration of the injured nerves were then studied by RNA sequencing and proteomic techniques. In the tibial and common peroneal nerves, there were 1718, 1374, 1187, and 2195 differentially expressed genes, and 477, 447, 619, and 495 differentially expressed proteins on days 1, 7, 14, and 21 after surgery, respectively. Forty-seven pathways were activated during Wallerian degeneration. Three genes showing significant differential expression by RNA sequencing (Hoxd4, Lpcat4 and Tbx1) were assayed by real-time quantitative polymerase chain reaction. RNA sequencing and real-time quantitative polymerase chain reaction results were consistent. Our findings showed that expression of genes and proteins in injured tibial and the common peroneal nerves were significantly different during Walleri-an degeneration at different time points. This suggests that the biological processes during Wallerian degeneration are different in different peripheral nerves after injury. The procedure was approved by the Animal Experimental Ethics Committee of the Second Military Medical University, China (approval No. CZ20160218) on February 18, 2016.