【Abstract】 Objective To investigate the effects of isoliquiritigenin (ISL) on the inflammatory response and Th1/Th2 cell imbalance after traumatic brain injury (TBI) in rats through the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) pathway. MethodsSPF rats were randomly divided into model group，low-dose of ISL group (20 mg·kg-1)，highdose of ISL group (40 mg·kg-1)，positive drug group (glycerol fructose sodium chloride，40 mg·kg-1)，and control group，with 10 rats in each group. Histopathological changes of rat brain were observed by HE staining. Serum levels of interleukin-1β (IL-1β)，interleukin-4 (IL-4)，interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) were compared. TLR4，MyD88，NF-κB p65 mRNA and TLR4，MyD88，NF-κB p65，phosphorylated nuclear transcription factor-κB p65 (p-NF-κB p65) protein expression in brain tissue. ResultsCompared with the control group，the levels of serum IL-1β，IL-4 and TNF-α，TLR4，MyD88 mRNA，TLR4，MyD88 and p-NF-κB p65 protein in the brain tissue of model group were increased，and the level of serum IFN-γ was decreased (P<0.05). Compared with model group，the levels of serum IFN-γ，IL-1β，IL-4 and TNF-α，TLR4，MyD88 mRNA and protein levels of TLR4，MyD88 and p-NF-κB p65 in low-dose of ISL and high-dose of ISL groups were increased in positive drug group (P<0.05). Compared with low-dose of ISL group，the levels of serum IFN-γ，IL-1β，IL-4，TNF-α，TLR4，MyD88 mRNA and protein levels of TLR4，MyD88，p-NF-κB p65 in high-dose of ISL group and positive drug group were increased (P<0.05). Compared with highdose of ISL group，serum IFN-γ level was increased，IL-1β，IL-4，TNF-α level，TLR4，MyD88 mRNA level and TLR4，MyD88，p-NF-κB p65 protein level were decreased in positive drug group (P<0.05). HE Results showed that the brain tissue lesions in the positive drug group were improved in different degrees compared with the model group in the low and high dose of ISL groups，especially in the high dose of ISL group and the positive drug group. ConclusionISL can effectively improve the inflammatory response of TBI in rats and regulate Th1/Th2 cell balance，which may be based on the regulation of TLR4/MyD88/NF-κB pathway related mRNA and protein expression.