Objective Applied mast cell stabilizers to investigate the role of central nervous system (CNS)mast cells in 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 factorα(TNF-α), interleukin( IL-6), corticotropin releasing hormone(CRH), thyroid-stimulating hormone(TSH), adreno-cortico-tropic-hormone, cortisol, triiodothyronine(T3) and thyroxine (T4) were measured with a commercial ELISA kit. Cell signaling proteins were analyzed by Western blotting. 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, Serine-threonine kinase (AKT),and nuclear factor-κB (NF-κB)signaling pathway activation in vivo. Stabilization of central nervous system mast cells also alleviates LPS-induced decrease of thyroid-stimulating hormone and triiodothyronine levels, and increase of thyroxinelevel in the peripheral blood and brain hypothalamus. Conclusions Stabilization of central nervous system mast cells was able to delay the pathogenesis of LPS-induced liver inflammation, which was participated by the hypothalamic-pituitary-thyroid axis.