Background and Objective: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various immunological abnormalities. Triptolide is a diterpene triepoxide antibiotic compound that can be isolated from extracts of the medicinal plant, Tripterygium wilfordii Hook F., which has been used for a number of years in traditional Chinese medicine. Triptolide have immunosuppressive and anti-inflammatory properties. The present study aimed to determine the effects of triptolide on lupus-prone MRL/lpr mice. Materials and Methods: MRL/lpr mice were divided into two groups, including model control group and triptolide-treated group. Mice were administered for 8 weeks by oral gavage. Eight weeks after treatment, the mice serum levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) were measured with ELISA. The kidney damage of MRL/lpr mice was examined with haematoxylin and eosin (HE) staining and immunofluorescence of deposition of IgG and IgM in glomeruli. Gene expression levels of Toll-like receptor (TLR9), Toll-like receptor 4 (TLR4) and Nuclear factor-κB (NF-κB) in kidney of MRL/lpr mice were measured using real-time PCR. One-way ANOVA, followed by Newman-Keuls test or Student's t-test were used. Results: The results showed that triptolide improved skin damage, decreased the serum levels of IFN-γ and IL-10 in MRL/lpr mice. Moreover, triptolide could improve renal histopathologic characteristics of MRL/lpr mice and downregulate the mRNA level of TLR9, TLR4 and NF-κB. Conclusion: These findings indicated that triptolide might have the potential therapeutic utility for the treatment of SLE.