Abstract: ObjectiveTo investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model. Methods Ten wild type mice and 40 MRL/lpr mice were used in this stuy. MRL/lpr mice were randomly assigned to MRL/lpr group, MRL/lpr + dexamethasone (1.5 mg/kg) group, MRL/lpr + paeoniflorin (20 mg/kg) group, and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde（MDA），superoxide dismutase (SOD）, catalase (CAT）, glutathione peroxidase (GSH-Px） in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K), phospho-serine-threonine kinase B(P-Akt）, phospho-nuclear factor kappa B (P-NF-κB), phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot. Results Paeoniflorin decreased serum level of MDA and increased the levels of SOD, CAT, GSH-PX, and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K, P-Akt, P-NF-κBp65, and P-IκBα in the lung tissue of MRL/lpr mice. Conclusion Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.