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Background: Clinically, the condition of skeletal muscle injury is the key to the process of high voltage electrical burn (HVEB) wound repair. The aim of this study was to identify the potential mechanisms and intervention targets of skeletal muscle injury after HVEB., Methods: A skeletal muscle injury model in SD rats with HVEB was made. Pathological examination and transcriptome sequencing of injured skeletal muscles were performed, and the expression levels of key proteins and genes in related signaling pathways were verified., Results: Skeletal muscle injury was progressively aggravated within 48 h, then the injury was gradually repaired with scar formation occurring within 1 week. The mechanism of skeletal muscle injury is complex and varied, and ferroptosis is one of the mechanisms. The ferrous iron content in the injured skeletal muscle tissue of model rats increased significantly at 24 h after injury. After 24 h, damage to injured skeletal muscle tissue could be alleviated by increasing iron storage and blocking lysosomal phagocytosis of autophagy., Conclusions: Skeletal muscle injury caused by HVEB is characterized by adjacent endangered tissue progression after injury. Ferroptosis is involved in the mechanism of HVEB, and iron metabolism-related proteins may be potential targets for preventing progressive skeletal muscle injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)