The immunosuppressive properties of an aqueous suspension of Withania somnifera (WS) root powder were investigated in a pristine induced female Balb/c model of a systemic lupus erythematosus (SLE) like disease. The course of disease is initiated by peritoneal inflammation caused by pristane which results in development of SLE like symptoms, i.e. autoantibody production, proteinuria, and nephritis within a period of five to six months. The model of SLE was established by injecting 0.5 mL of pristane intraperitoneally into female Balb/c mice (12-18 weeks old). WS root powder (500 mg and 1,000 mg per kg body weight) was administered orally from one month prior to disease induction and for the following 6 months. Parameters of inflammation like nitric oxide (NO), Interleukin 6 and tumour necrosis factor-α and reactive oxygen species (ROS) in serum and/or ascitic fluid were measured. Prophylactic administration of WS root powder (500 mg and 1,000 mg per kg body weight) potently inhibits the proinflammatory cytokines, NO, and ROS in the ascetic fluid as well as in serum. Therefore, our results indicate a preventive effect of WS root powder on the mouse model of lupus.