Abstract: Objective: To investigate the protective effect of Baihe Wuyao decoction (BWD) on mice with type 1 diabetes mellitus (T1DM) and liver damage, and to reveal its underlying mechanism. Methods: Ten of 70 mice were randomly selected as the blank group, and the rest were induced with intra-peritoneally (ip) streptozotocin (STZ) to induce T1DM. After successful modeling, the mice were randomly divided into 6 groups: Model group, positive control group and BWD groups (15, 5, 2.5, 1.25 g·kg⁻¹·d⁻¹). The mice in each group were given continuous administration for 6 weeks. The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of mice were measured, and the contents of superoxidedismutase (SOD) and malonaldehyde (MDA) in liver tissue homogenate were detected. The pathological changes of mouse liver were observed. The expression of Protein kinase B (AKT) in mouse liver was detected, the mRNA level of manganese superoxide dismutase (Mn-SOD) and nitric oxide synthase (iNOS), inflammatory factors including tumor necrosis factor (TNF-α), nuclear factor-κB (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), apoptosis factors including B-cell lymphoma-2 (Bcl2), Bcl2-associated X protein (Bax), Caspase 3 (CASP3) were measured. Results: BWD exhibited a good hepatic protection with ameliorating hepatic pathological morphology in T1DM mice. Compared with the model group, the levels of ALT and AST in each dose group were significantly reduced (P<0.01, P<0.05), and the effect of the low 1 dose group was more obvious. The low 1 dose of BWD could significantly up-regulate p-AKT/AKT(P<0.05), low dose 1 could significantly down-regulate MDA, iNOS, and up-regulate SOD and Mn-SOD content(P<0.01, P<0.05). Comparing with the model group, the ratio of Bcl2/Bax at the low dose increased significantly, Bax and CASP3 were down-regulated, the low dose significantly reduced the expression of TNF-α, NF-κB, IL-1β, IL-6 and IL-8 at the gene level (P<0.01, P<0.05). Conclusion: The BWD would have a good hepatic protective effect during T1DM, which underlying mechanisms through improving insulin resistance and suppresses oxidative stress, apoptosis, inflammation and promotion of cell proliferation.