BackgroundSpinal cord injury (SCI), which reportedly induces severe motor dysfunction, imposes a significant social and financial burden on affected individuals, families, communities, and nations. Acupuncture combined with moxibustion (AM) therapy has been widely used for motor dysfunction treatment, but the underlying mechanisms remain unknown. In this work, we aimed to determine whether AM therapy could alleviate motor impairment post-SCI and, if so, the potential mechanism.MethodsA SCI model was established in mice through impact methods. AM treatment was performed in SCI model mice at Dazhui (GV14) and Jiaji points (T7-T12), Mingmen (GV4), Zusanli (ST36), and Ciliao (BL32) on both sides for 30 min once per day for 28 days. The Basso–Beattie–Bresnahan score was used to assess motor function in mice. A series of experiments including astrocytes activation detected by immunofluorescence, the roles of NOD-like receptor pyrin domain-containing-3 (NLRP3)–IL-18 signaling pathway with the application of astrocyte-specific NLRP3 knockout mice, and western blot were performed to explore the specific mechanism of AM treatment in SCI.ResultsOur data indicated that mice with SCI exposure exhibited motor dysfunction, a significant decrease of neuronal cells, a remarkable activation of astrocytes and microglia, an increase of IL-6, TNF-α, IL-18 expression, and an elevation of IL-18 colocalized with astrocytes, while astrocytes-specific NLRP3 knockout heavily reversed these changes. Besides, AM treatment simulated the neuroprotective effects of astrocyte-specific NLRP3 knockout, whereas an activator of NLRP3 nigericin partially reversed the AM neuroprotective effects.ConclusionAM treatment mitigates SCI-induced motor dysfunction in mice; this protective mechanism may be related to the NLRP3–IL18 signaling pathway inhibition in astrocytes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13018-023-03902-6.