Objective：Applied mast cell stabilizers to investigate the role of central nervous system（CNS） mast cells in lipopolysaccharide（LPS）-induced liver inflammation. Methods：Stabilized brain mast cells by site-directed injection of cromolyn in rat right hypothalamus using stereotaxic techniques in vivo. Liver histopathological changes were evaluated by hematoxylin and eosin staining. Tumor necrosis factor α（TNF-α），interleukin 6（IL-6），thyroid-stimulating hormone（TSH），triiodothyronine（T3），and thyroxine（T4）were measured with commercial ELISA kits. Cell signaling proteins were analyzed by Western blot. Results：LPS administration induced increase of serum TNF-α and IL-6 levels，liver pathology and mitogen activated protein kinases（MAPK），serine-threonine kinase（AKT），and nuclear factor-κB（NF-κB）signaling activation. Furthermore，stabilization of CNS mast cells can ameliorate LPS-induced liver inflammation and MAPK，AKT，and NF-κB signaling pathway activation in vivo. Stabilization of CNS mast cells also alleviated LPS-induced decrease of TSH and T3 levels，and increase of T4 level in the peripheral blood and brain hypothalamus. Conclusion：Stabilization of CNS mast cells can delay the pathogenesis of LPS-induced liver inflammation，which is participated by the hypothalamic-pituitary-thyroid axis.