Abstract: This study investigated the material basis of Huoluoxiaolingdan in treating diabetic peripheral neuropathy (DPN) through ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and network pharmacology. UPLC-Q-TOF-MS/MS combined with PeakView^TM 1.2 software and Molecule Profiler^TM software were used to analyze the the chemical components of Huoluoxiaolingdan and blood-absorbed ingredients in normal rats and rats with DPN induced by high fat diet combined with low dose streptozotocin injection. Swiss Target Prediction database, GeneCards and other databases were used to search the corresponding targets of active ingredients and disease targets. The intersection targets were obtained using Venny 2.1 platform, which were then imported into the STRING platform and Cytoscape 3.10.1 software to construct the protein-protein interaction network and the "component-target" network relationship diagram, and the core components and core targets were analyzed. GO and KEGG pathway enrichment analysis of key targets were performed. All experiments were approved by the experimental Animal Ethics Committee from Nanjing University of Chinese Medicine (No. 202310A023). A total of 83 chemical components were identified, including 52 terpenoids such as tanshinone Ⅱ_A, 11 phthalides such as Z-ligustilide, 15 organic acids such as ferulic acid, 4 coumarins and 1 phenol. Additionally, 15 prototype components and 29 metabolites were identified in normal rats' plasma, and 17 prototype components and 32 metabolites were identified in DPN rats' plasma. Network pharmacology results show that 5 core components such as 3-acetyl-11-keto-β-boswellic acid and 11-keto-β-boswellic acid may act through 27 core targets such as TNF and IL6 to regulate AGE-RAGE and PI3K/Akt and other signaling pathways so as to play a therapeutic role in treatment of DPN. The study efficiently analyzed the constituents in vitro and blood-absorbed ingredients of Huoluoxiaolingdan and the cracking regularity of the main compounds, and the core components of its treatment of DPN were analyzed in combination with network pharmacology, which can provide reference for further research of the pharmacodynamic substantial basis and mechanism of Huoluoxiaolingdan in the treatment of DPN.