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This study found that after spinal cord injury, macrophages phagocytize myelin debris to form foamy macrophages, while microglia do not form foamy cells, which may be because microglia can effectively clear myelin debris in a relatively short time, whereas macrophages cannot. In addition, we found that ACAT1 did not mediate the formation of foamy macrophages after spinal cord injury, which was different from atherosclerosis. This study demonstrates that microglia have a stronger ability to clear myelin debris than macrophages and may contribute to the development of novel therapeutic strategies to remove myelin debris more effectively, reduce inflammatory responses, promote remyelination, and accelerate functional recovery after spinal cord injury.