Salvianolic acid B (Sal B), a water-soluble compound from *Salvia miltiorrhiza Bunge*, exhibits anti-inflammatory and anti-fibrotic properties. This study investigates how Sal B alleviates liver injury by regulating lactate-mediated histone lactylation in macrophages. In an LPS-induced M1 macrophage model, Sal B significantly reduced the expression of inflammatory factors and M1 polarization markers. It downregulated lactate dehydrogenase A (LDHA), which is crucial for lactate production, and inhibited histone H3 lysine 18 (H3K18la) lactylation. Sal B reduced H3K18la levels in the promoter regions of LDHA, NLRP3, and IL-1β genes, suggesting it suppresses the NLRP3 inflammasome pathway. In vivo experiments showed that Sal B alleviated carbon tetrachloride (CCl₄)-induced liver injury by reducing macrophage M1 polarization and histone lactylation. Kupffer cells isolated from Sal B-treated livers also showed reduced lactate and histone lactylation. These findings indicate that Sal B mitigates liver injury by inhibiting histone lactylation through LDHA downregulation, thereby suppressing macrophage inflammation and polarization. The study highlights the potential of targeting histone lactylation as a therapeutic strategy for liver fibrosis.Salvianolic acid B (Sal B), a water-soluble compound from *Salvia miltiorrhiza Bunge*, exhibits anti-inflammatory and anti-fibrotic properties. This study investigates how Sal B alleviates liver injury by regulating lactate-mediated histone lactylation in macrophages. In an LPS-induced M1 macrophage model, Sal B significantly reduced the expression of inflammatory factors and M1 polarization markers. It downregulated lactate dehydrogenase A (LDHA), which is crucial for lactate production, and inhibited histone H3 lysine 18 (H3K18la) lactylation. Sal B reduced H3K18la levels in the promoter regions of LDHA, NLRP3, and IL-1β genes, suggesting it suppresses the NLRP3 inflammasome pathway. In vivo experiments showed that Sal B alleviated carbon tetrachloride (CCl₄)-induced liver injury by reducing macrophage M1 polarization and histone lactylation. Kupffer cells isolated from Sal B-treated livers also showed reduced lactate and histone lactylation. These findings indicate that Sal B mitigates liver injury by inhibiting histone lactylation through LDHA downregulation, thereby suppressing macrophage inflammation and polarization. The study highlights the potential of targeting histone lactylation as a therapeutic strategy for liver fibrosis.