Objective To investigate the effects and potential mechanisms of B-cell activating factor (BAFF) on oxidative stress and inflammatory response in a mouse model of immune thrombocytopenia (ITP). Methods Guinea pig anti-mouse platelet antiserum (GP-APS) was prepared, and 50 specific pathogen-free adult male BALB/c mice (7-8 weeks old) were randomly divided into 5 groups with n=10 in each group. The groups included a control group (blank control), an ITP group (induced by GP-APS), an ITP+rhBAFF group (ITP combined with intravenous injection of 50 μg/kg/50 μL recombinant human BAFF protein). Recombinant adenovirus vectors silencing Dll1 (shDll1) and Jagged1 (shJagged1) were constructed, and adenovirus vectors were intravenously injected on top of the ITP+rhBAFF group once a day for 1 week, named the ITP+rhBAFF+shDll1 (100 μg/kg) group and ITP+rhBAFF+shJagged1 (25 μg/kg) group, respectively. After 1 week, peripheral blood was collected from the mice and peripheral blood mononuclear cells and serum were separated. Platelet counts in peripheral blood were measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of BAFF, Dll1, Jagged1, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) in mouse serum. Pearson correlation analysis was used to analyze the correlation between BAFF and Dll1, Jagged1 levels in peripheral blood serum. Western blot was performed to detect the protein expression of BAFF, Dll1, and Jagged1 in peripheral blood mononuclear cells. Results Compared to the control group, the peripheral blood platelet count in the ITP group of mice was significantly reduced (P＜0.05). There was a significant negative correlation between the peripheral blood platelet count in ITP mice and the level of BAFF (r=-0.5687; P=0.0338, 95% CI: -0.8445 to -0.05464). Similarly, a significant negative correlation was observed between the peripheral blood platelet count and the level of Dll1 (r=-0.6361; P=0.0145, 95% CI:-0.8723 to -0.1592), as well as between the peripheral blood platelet count and the level of Jagged1 (r=-0.6409; P=0.0135, 95% CI:-0.8742 to -0.1672).The level of BAFF in peripheral blood of ITP mice was positively correlated with Dll1 (r=0.5794; P=0.0236, 95%CI:0.09544-0.8418). The level of BAFF was significantly positively correlated with Jagged1 (r=0.5723; P=0.0258, 95%CI:0.08489-0.8387). Compared with the control group, the levels of BAFF, Dll1, Jagged1, IL-1β, IL-6, TNF-α, ROS, MDA were upregulated, and the levels of GSH-PX and SOD were downregulated in the peripheral blood of the ITP group (P＜0.05). Compared with the ITP group, the levels of BAFF, Dll1, Jagged1, IL-1β, IL-6, TNF-α, ROS, MDA were upregulated, platelet count was decreased, and the levels of GSH-PX and SOD were downregulated in the peripheral blood of the ITP+rhBAFF group (P＜0.05). Compared with the ITP+rhBAFF group, the levels of Dll1, Jagged1, IL-1β, IL-6, TNF-α, ROS, MDA were downregulated, platelet count was increased, and the levels of GSH-PX and SOD were upregulated in the peripheral blood of the ITP+rhBAFF+shDll1 group (P＜0.05). Compared with the ITP+rhBAFF group, the levels of Jagged1, IL-1β, IL-6, TNF-α, ROS, MDA were downregulated, platelet count was increased, and the levels of GSH-PX and SOD were upregulated in the peripheral blood of the ITP+rhBAFF+shJagged1 group (P＜0.05). Conclusion BAFF promotes oxidative stress and inflammatory response in a mouse model of immune thrombocytopenia by activating the Dll1/Jagged1 signaling pathway