<p>Spinal cord injury (SCI) is characterized by macrostructural pathological changes in areas significantly distant from the primary injury site. The causes and mechanisms underlying these distant changes are still being explored. Identifying the causes and mechanisms of these changes in the lumbar spinal cord is particularly important for restoring motor function, especially in cases of injury to the proximal thoracic or cervical regions. This is because the lumbar region contains neural networks that play a crucial role in comprehensive locomotor outcomes. In our study, we investigated the changes in the rat lumbar spinal cord following a thoracic contusion injury. We observed an increased expression of osteopontin (OPN) in large neurons and a higher number of interneurons co-expressing parvalbumin and OPN within lamina IX of the ventral horns (VH) in the gray matter of the lumbar spinal cord post-injury. Additionally, here we noted an increased co-localization of the glial fibirillary acidic protein and S100A10 protein, a specific marker of reactive A2 astrocytes. Our findings also include changes in the expression and content of glypicans in the gray matter, a significant rise in neurotoxic M1 microglia/macrophages, alterations in the cytokine profile, and a decreased expression of the extracellular matrix molecules tenascin R and aggrecan. This research highlights the complex pathological processes occurring far from the site of SCI and attempts to provide insights into the mechanisms involving the entire spinal cord in the response to such an injury.</p>