Abstract: ob＜x＞jective To study the molecular mechanism of Exendin-4 in repairing peripheral nerve injury (PNI) nerve regeneration through bioinformatics and molecular biology, and provide potenti al therapeutic targets for PNI. Methods High-throughput gene chip technology was used to monitor the gene changes of distal sciatic nerve injury in mice before and after Exendin-4 treatment, and the differential genes were screened by bioinformatics method. The differential genes were analyzed by GO enrichment analysis and PPI network analysis to elucidate the molecular mechanism of Exendin-4 in repairing PNI nerve regeneration. In addition, we further verified the peripheral nerve repair mechanism of Exendin-4 by molecular biology. Results A total of 180 genes with significant ex＜x＞pression differences were detected (P < 0.05; FC ≤ 0.5 or ≥ 2). Among them, 146 were raised and 34 were lowered. The results of GO analysis focused on histone H4 acetylation, histone acetyltransferase activity, histone acetyltransferase complex, ubiquitin-specific protease activity, ubiquitin hydrolase activity, Ubiquitin-specific protease activity and protein deubiquitination. According to PPI network analysis, the key gene: Matrix me＜x＞talloproteinase-9 (Mmp9) showed the highest Degree of correlation, and Exendin-4 had the greatest correlation with PNI repair nerve regeneration. The results of QPCR and Western blot showed that the mRNA and protein ex＜x＞pression levels of Mmp9 were significantly increased after Exendin-4 injection in schwann cells . Conclusion The results of this study indicate that Exendin-4 promotes the proliferation and migration of Schwann cells through MMP9, thereby improving the ability of nerve regeneration. Therefore Therefore, our stydy provide a new insight in repairing peripheral nerve injury.