【Abstract】Objective To investigate the effects of Bilobalide (BB) on Toll like receptor-4 (TLR4)/nuclear factor- kappa B (NF-κB) signaling pathway and helper T lymphocyte 1/2(Th1/Th2) in sepsis induced acute lung injury (ALI) rats. Methods Fifty SD rats were randomly divided into sham operation group (sham group), model group (ALI group), BB low (2.5 mg/kg) dose group, BB high dose (10 mg/kg) group and dexamethasone positive control group (0.45 mg/kg). Except for sham group, the other groups were made into Ali model by cecal ligation and puncture. 6 hours after operation, the corresponding dose of drugs was injected into caudal vein in each drug group In group I, normal saline was injected through caudal vein for 3 days. After the last administration of 1H, the rats were sacrificed and the lung tissues were taken. Hematoxylin eosin staining (HE) was used to detect the pathological changes of lung tissue in each group. Enzyme linked immunosorbent assay (ELISA) kit was used to detect the activity of lung tissue MPO, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF alpha) level, and the lung tissue was detected by electrophoretic mobility shift assay (EMSA). The expression of TLR4 pathway protein in lung tissue was detected by Western blot, and the ratio of helper T cell 1/2(Th1/Th2) in lung cells was detected by flow cytometry (FACS).Results Compared with sham group, ALI group showed edema, inflammatory cell infiltration and other pathological damage. The contents of MPO, IL-6, TNF-α, TLR4 Protein Expression and NF-κB activity were significantly increased in ALI group (P＜0.05), while Th1/Th2 and TNF-α/IL-6 were significantly decreased in ALI group (P＜0.05). Compared with ALI group, pulmonary edema and inflammatory cell infiltration were alleviated in BB low and high dose groups and dexamethasone positive group. MPO, IL-6, TNF-α content, TLR4 Protein Expression and NF-κB activity in lung tissue were significantly decreased (P＜0.05), Th1/Th2 and TNF-α/IL-6 were significantly increased (P＜0.05). Compared with low-dose BB group, pulmonary edema and inflammatory cell infiltration in high-dose BB group and dexamethasone positive group were significantly reduced, MPO, IL-6, TNF-α content, TLR4 Protein Expression and NF-κB activity were significantly decreased (P＜0.05), Th1/Th2 and TNFα/IL6 were significantly increased (P＜0.05).Conclusion BB can inhibit the activation of TLR4/NF-κB signal pathway, regulate the balance of Th1/Th2, reduce the release of inflammatory mediators, and improve the lung injury in sepsis ALI rats.