BACKGROUND: Inflammation at the injury site exacerbates tissue cell death following a spinal cord injury (SCI). Studies show that NLRP3 inflammasomes are crucial in the inflammation following Spinal Cord Injury, and NLRP3 inflammasomes have been shown to promote cells to undergo excessive autophagy in other diseases. Moreover, excessive autophagy levels could hinder functional repair post-SCI. In this regard, we hypothesized that inhibiting NLRP3 inflammasomes could reduce autophagy levels at the injury site, thus promoting functional repair post-SCI. METHODS: Herein, a mouse SCI model was used for in vivo experiments, and an in vitro neuroinflammatory model created using LPS-activated BV2 cells was used for in vitro experiments. Histopathological staining was used to assess tissue repair. Western Blot (WB) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) were used to detect changes in relevant autophagy molecules, macrophage polarization-related markers and downstream inflammatory factors, and Immunofluorescence (IF) was used to detect changes in macrophage polarization. RESULTS: Following SCI, the inhibition of NLRP3 inflammasomes resulting from intraperitoneal injection of MCC950 significantly reduced autophagy levels at the injury site, resulting in both histological and behavioral improvements. In addition, the phosphorylation of mTOR during inhibition of NLRP3 inflammasomes to reduce autophagy levels further improved the immune microenvironment at the injury site, and M2-type macrophages were significantly upregulated M2-type macrophages. Moreover, in vitro experiments yielded results consistent with those of in vivo experiments regarding changes in autophagy-related indexes and polarization-related markers. CONCLUSIONS: Inhibition of NLRP3 inflammasomes can reduce autophagy level at the injury site to promote functional recovery and play a neuroprotective role. Moreover, phosphorylation of mTOR during the process of inhibition of NLRP3 inflammasomes to reduce autophagy, leading to reduced autophagy levels, could improve the immune microenvironment at the injury site, thus promoting functional recovery and histopathological repair post-SCI.