This study aimed to assess the therapeutic effects of Wu-Di-Tang (WDT) on lupus prone MRL/lpr mice and provide an experimental basis for clinical applications. Thirty-two female MRL/lpr mice were randomly assigned to treatment and control groups, 16 in each group. Oral administration of WDT and saline to treated and control mice began from 12 weeks of age and continued for 16 weeks. The efficacy of WDT was evaluated by assessing survival rate, lymphadenopathy, C-reactive protein (CRP), proteinuria, serum creatinine and dsDNA autoantibody in continuous samples taken at different time points (12, 16, 20, 24 and 28 weeks), and pathological changes of the kidneys at 28 weeks. WDT effectively prolonged the survival of lupus mice, inhibited the production of serum anti-dsDNA autoantibody (p < 0.05, 0.01), reduced lymph node enlargement (p < 0.05, 0.01, 0.001) and serum CRP (p < 0.01), decreased the levels of proteinuria and serum creatinine (p < 0.05, 0.01, 0.001), and ameliorated the pathology of lupoid nephritis in treated mice compared to control animals. These data indicate that WDT has the potential to regulate the immune system, inhibit inflammatory reactions, improve kidney function, and ultimately produce beneficial effects on Systemic lupus erythematosus (SLE) mice. Moreover, it is promising for WDT to be developed as a novel immunotherapeutic agent to treat SLE.