OBJECTIVE：To study the protective effects of cyclosporine on renal tissue of pristine-induced systemic lupus erythematosus （SLE） model mice and its mechanism. METHODS：Female BALB/c mice was given pristine 0.5 mL intraperitoneally to establish SLE model. The levels of urine protein and anti-ds-DNA antibody were detected to validate model establishment. 6 months later，40 model mice were randomly divided into model group，positive control group （prednisone，5 mg/kg），cyclosporine high-dose and low-dose groups （30，10 mg/kg），once a day，5 times a week，for consecutive 18 weeks. Another 10 un-modeled mice were included in normal control group and given normal saline intragastrically. The serum levels of immunological indexes as anti-ds-DNA antibody，IgG，IgM and inflammatory factors such as TNF-α，IL-6 and IFN-γ were detected by ELISA. 24 h urine protein and serum creatinine （Cr），urea nitrogen （BUN） levels were measured by biochemical method. The pathological changes of renal tissues were observed by HE staining. Immunohistochemistry was used to survey IgG immune complexes deposition in renal tissues. mRNA expression of p38MAPK and TWEAK were detected by RT-PCR. RESULTS： Compared with normal control group，the serum levels of anti-ds-DNA，IgG，IgM，TNF-α，IL-6，IFN-γ，Cr，BUN and 24 h urine protein in mice were significantly increased in model group （P＜0.05）；obvious pathological changes were observed in renal tissue and the expression level of IgG immune complex increased significantly （P＜0.05）； the mRNA expression levels of p38MAPK and TWEAK in renal tissue were increased significantly （P＜0.05）. Compared with model group，the serum levels of anti-ds-DNA，IgG，IgM，TNF-α，IL-6，IFN-γ，Cr，BUN and 24 h urine protein were significantly decreased in cyclosporine high-dose group，and the serum levels of anti-ds-DNA，IgG and BUN were also significantly decreased in cyclosporine low-dose group （P＜0.05）； the pathological changes of renal tissue were relieved significantly in cyclosporine high-dose and low-dose groups，and expression levels of IgG immune complex were decreased significantly （P＜0.05）； the mRNA expression levels of p38MAPK and TWEAK in renal tissue were decreased significantly in cyclosporine high-dose group，and those of TWEAK were also decreased significantly in cyclosporine low-dose group（P＜0.05）. CONCLUSIONS：Cyclosporine has certain protective effect on renal tissue of pristine-induced SLE model mice and can relieve renal injury to certain extent，which may be associated with inhibiting TWEAK-p38MAPK signaling pathway.