<p>Spinal cord injury is a disease with no complete cure. It typically results in loss of motor and sensory functions below the level of the lesion, leading to significant physical and psychological disorders. After spinal cord injury, the microenvironmental balance at the site of injury is disrupted, creating complex conditions that are not conducive to nerve regeneration and recovery of spinal cord function, such as hemorrhage and ischemia, glial scar formation, and nerve demyelination. As our knowledge of the spinal cord microenvironment has expanded, researchers have determined that therapeutic strategies that modulate the microenvironment represent a significant and efficacious avenue of investigation. This review summarizes the characteristics of microenvironmental changes at various stages after spinal cord injury. Additionally, it discusses novel strategies developed recently based on regulating the microenvironment after spinal cord injury to promote recovery. The investigation of a long-acting, targeted, and multitemporal combination therapy strategy to repair spinal cord injuries shows promise in terms of its developmental potential.</p> Graphical Abstract <p></p> <p>A schematic overview of changes of microenvironment components after SCI and strategies for reconstructing microenvironment.<i> NISCI</i> Non-traumatic spinal cord injury,<i> SCI</i> Spinal cord injury<i>TSCI</i> Traumatic spinal cord injury. Created with biorender.com</p>