It is often difficult to regain neurological function following spinal cord injury (SCI). Neuroinflammation is thought to be responsible for this failure. Regulating the inflammatory response post-SCI may contribute to the recovery of neurological function. Over the past few decades, studies have found that macrophages/microglia are one of the primary effector cells in the inflammatory response following SCI. Growing evidence has documented that macrophages/microglia are plastic cells that can polarize in response to microenvironmental signals into M1 and M2 macrophages/microglia. M1 produces pro-inflammatory cytokines to induce inflammation and worsen tissue damage, while M2 has anti-inflammatory activities in wound healing and tissue regeneration. Recent studies have indicated that the transition from the M1 to the M2 phenotype of macrophage/microglia supports the regression of inflammation and tissue repair. Here, we will review the role of the inflammatory response and macrophages/microglia in SCI and repair. In addition, we will discuss potential molecular mechanisms that induce macrophage/microglia polarization, with emphasis on neuroprotective therapies that modulate macrophage/microglia polarization, which will provide new insights into therapeutic strategies for SCI.