Liver fibrosis, a critical pathological feature of chronic liver injury, is closely associated with macrophage-mediated inflammatory responses and metabolic reprogramming. Blocking the fibrosis process will be beneficial to the treatment and recovery of the disease. Liver macrophages are a remarkably heterogeneous population of immune cells that play multiple functions in homeostasis and are central to liver fibrosis. Glycolysis-mediated macrophage metabolic reprogramming leads to an increase in the proportion of M1 macrophages and the release of pro-inflammatory cytokines. The present study aimed to investigate the therapeutic effect and mechanism of acid B (SAL B) against carbon tetrachloride (CCl(4))-induced liver fibrosis. Here, we demonstrate that SAL B reduced the production of inflammatory factors in CCl(4)-induced liver fibrosis. Mechanistically, SAL B increased the expression of migration inhibitor 1 (MIG1) by inhibiting DNMT1-mediated methylation of the MIG1 promoter. Subsequently, MIG1 reduced the transcription of lactate dehydrogenase A (LDHA) and hexokinase 2 (HK2) which blocked glycolysis-mediated macrophage M1 polarization. In summary, our results suggested that SAL B is a promising intervention for ameliorating liver fibrosis.