Salvianolic acid B (Sal B) is a water-soluble bioactive compound derived from *Salvia miltiorrhiza* Bunge, known for its anti-inflammatory and anti-fibrotic properties. This study aimed to investigate the mechanism by which Sal B alleviates liver injury through macrophage regulation. In an LPS-induced M1 macrophage model, Sal B showed a dose-dependent inhibition of macrophage polarization. Sal B downregulated lactate dehydrogenase A (LDHA) expression, which is crucial for lactate production, and overexpression of LDHA impaired Sal B's effect on macrophage polarization. Additionally, Sal B inhibited histone H3 lysine 18 (H3K18Ia) lactylation, a key epigenetic modification involved in gene transcription. ChIP-qPCR analysis confirmed that Sal B reduced H3K18Ia levels in the promoter regions of LDHA, NLRP3, and IL-1β genes. In vivo experiments using a CCl4-induced liver injury model in mice demonstrated that Sal B effectively alleviated liver injury and reduced inflammation and fibrosis. The study concluded that Sal B inhibits macrophage polarization and histone lactylation, thereby reducing inflammatory responses and protecting against liver injury.Salvianolic acid B (Sal B) is a water-soluble bioactive compound derived from *Salvia miltiorrhiza* Bunge, known for its anti-inflammatory and anti-fibrotic properties. This study aimed to investigate the mechanism by which Sal B alleviates liver injury through macrophage regulation. In an LPS-induced M1 macrophage model, Sal B showed a dose-dependent inhibition of macrophage polarization. Sal B downregulated lactate dehydrogenase A (LDHA) expression, which is crucial for lactate production, and overexpression of LDHA impaired Sal B's effect on macrophage polarization. Additionally, Sal B inhibited histone H3 lysine 18 (H3K18Ia) lactylation, a key epigenetic modification involved in gene transcription. ChIP-qPCR analysis confirmed that Sal B reduced H3K18Ia levels in the promoter regions of LDHA, NLRP3, and IL-1β genes. In vivo experiments using a CCl4-induced liver injury model in mice demonstrated that Sal B effectively alleviated liver injury and reduced inflammation and fibrosis. The study concluded that Sal B inhibits macrophage polarization and histone lactylation, thereby reducing inflammatory responses and protecting against liver injury.