Abstract: Objective: The concoction process of vinegar roasted Chai Hu was optimized to investigate the hepatoprotective effect of Chai Hu before and after vinegar roasting on acute liver injury in mice. Methods: Combined with Box-Behnken response surface design method, the entropy weight method was applied. The indices of Saikosaponin A, Saikosaponin D and leachate were comprehensively scored to evaluate the vinegar dosage, smothering and wetting time and frying temperature so as to optimize the vinegar roasting process of Chai Hu. A model of acetaminophen (APAP)-induced acute liver injury in mice was established to analyze the effects on liver function, inflammation and oxidative stress before and after the vinegar roasting of Chai Hu. Results: The process parameters were 23% vinegar, 2.8 h smothering and wetting time and 145 ℃ frying temperature. The index contents were 0.65% Saikosaponin A, 0.74% Saikosaponin D and 20.67% leachate. In the Chai Hu vinegar group, the serum levels of mice were significantly reduced in alanine transaminase (ALT), glutathione transaminase (AST), tumour necrosis factor-α, interleukin-6, and interleukin-1β (P<0.05). In the liver tissues, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) increased respectively, and MDA significantly reduced (P<0.05). The Chai Hu group indicated insignificant improvement in GSH-Px and GSH. Conclusion: Entropy weight method combined with Box-Behnken response surface method optimized the process of the concoction of Northern Chai Hu with vinegar roasting was stable. With better effect than that of the Chai Hu group, vinegar Chai Hu can improve acute liver injury through inhibiting inflammation and lessening oxidative stress.