Systemic lupus erythematosus commonly known as lupus is an intricate disorder with multiple organ involvement characterized primarily by inflammation caused due to deposition of immune-complexes formed by production of autoantibodies against nuclear, nucleolar as well as cytoplasmic self-antigens. Lack of availability of suitable treatments or treatments that are only symptomatic calls for investigation of possible modalities. Withania somnifera with its immunomodulatory properties is prescribed for arthritis in ayurveda. In the present study, the therapeutic effect of Withania somnifera pure root powder (at 1,000 and 500 mg/kg body weight) on pristane-induced Balb/c model of lupus was investigated to elucidate its remedial outcome on SLE. SLE-like symptoms are produced in the model of lupus: production of autoantibodies, proteinuria, nephritis as well as immune-complex deposition along with various other inflammatory markers such as formation of lipogranuloma, production of pro-inflammatory cytokines including interleukin-6 and tumor necrosis factor-α, nitric oxide and reactive oxygen species. Withania somnifera was found to have potent inhibitory effect on proteinuria, nephritis and other inflammatory markers. Humoral response, however, was found to be impervious. The potent reduction in inflammation in the present model of lupus suggests further investigation of this herb for its possible therapeutic use in SLE.