OBJECTIVE: To observe the intervention of Chushizi(Fructus Broussonetiae)(CSZ) on drug-induced liver injury(DILI) in rats, as well as indicators of liver function, serum levels of inflammatory cytokines,and expression of proteins and m RNA associated with toll-like receptor 3(TLR3) and the signal transducer and activator of transcription 3(STAT3) pathway in the liver [TLR3, janus protein tyrosine kinase 2(JAK2), c-jun, c-fos, c-Jun N-terminal kinase 2(JNK2), and STAT3].METHODS: Forty specified pathogen free grade Sprague-Dawley rats were randomly divided into the control group, the model group, the silybin group and the CSZ group. Rats were given acetaminophen(APAP) to trigger DILI. Histopathology of the liver was observed by hematoxylin-eosin staining. The levels of alanine aminotransferase(ALT), aspartate transaminase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) in serum were detected by a semi-automatic biochemical instrument. Content of tumor necrosis factor alpha(TNF-α), interleukin(IL)-6, IL-13, and IL-22 in serum were detected by the enzyme-linked immunosorbent assay, the expression of TLR3, phosphorylation of JAK2(p-JAK2), while c-jun and c-fos proteins in the liver were determined by immunohistochemistry; expression of JNK2, and STAT3 in the liver were assayed by Western blot and real-time quantitative polymerase chain reaction. P-JNK2 and p-STAT3 in the liver were assayed by Western blot.RESULTS: After treatment, the activity of ALT, AST,and concentrations of TBIL, DBIL, TNF-α, IL-6, as well as IL-13 in serum, were lower than those in the model group, and expression of p-JAK2, TLR3,c-jun, c-fos, p-STAT3, and p-JNK2 could be downregulated.CONCLUSION: Our findings suggest that CSZ is a valid medicine to alleviate APAP-induced DILI,while its partial mechanism may regulate the TLR3/JNK/c-jun/c-fos/JAK/STAT3 pathway.