Objective: To study the effect of EPO therapy on liver injury, inflammation, oxidative stress and cell apoptosis in model rats with infection-induced acute liver injury. Methods: SD rats were selected and randomly divided into Sham group, sepsis group (CLP group) and EPO intervention group (EPO group), the cecal ligation and puncture was adopted to establish sepsis models and 5000IU/kg human recombinant EPO was provided for intervention. 24 hours after intervention, serum levels of liver injury molecules, inflammatory factors and oxidative stress molecules as well as liver tissue levels of oxidative stress molecules and cell apoptosis molecules were detected. >Results: Serum ALT, AST, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MDA and AOPP levels, liver tissue Nrf2, ARE, MDA and AOPP levels as well as Bax, Caspase-9 and Caspase-3 mRNA expression of CLP group were significantly higher than those of Sham group while liver tissue HO-1 and SOD levels as well as Bcl-2 mRNA expression were significantly lower than those of Sham group; serum ALT, AST, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MDA and AOPP levels, liver tissue MDA and AOPP levels as well as Bax, Caspase-9 and Caspase-3 mRNA expression of EPO group were significantly lower than those of CLP group while liver tissue Nrf2, ARE, HO-1 and SOD levels as well as Bcl-2 mRNA expression were significantly higher than those of CLP group. >Conclusions: EPO therapy could reduce liver injury and inhibit inflammation, oxidative stress and cell apoptosis in model rats with infection-induced acute liver injury.