Objective To observe the therapeutical effect and explore the underlying molecular mechamisms of specific cyclooxygenase-2 inhibitor(rofecoxib) on MRL/lpr mice.Methods 12-week female MRL/lpr mice were randomly assigned into following groups: the rofecoxib(10()mg·kg^{-1}·d^{-1}) for 12 weeks and the control group.Suppressive effect of the drugs on conjugate rate of serum anti-dsDNA antibody,serum angiotensin Ⅱ,thromboxanc B_2 and 6-keton-prostaglandin-F_{1α}levels were determined by using radio-immunological assay.The changes of proteinuria,serum creatinine and pathology in renal were also observed.Immunohistochemistry was used to examine the expression of TGF-β_1 and COX-2 in the kidney of MRL/lpr mice.Results Compared to the ones in the control group,mice treated with rofecoxib had lower levels of proteinuria(P<0.05),serum creatinine(P<0.05),the extracellular matrix reduced significantly(P<0.05),the expression of the positive of TGF-β_1 and COX-2 in renal tissue significantly decreased.Compared to the ones in the control group,mice treated with rofecoxib had lower levels of serum angiotensin II and thromboxanc B_2(P<0.05),while the levels of 6-keton-prostaglandin-F_{1α,}conjugate rate of serum anti-dsDNA antibody did not change(P>0.05).Conclusions Rofecoxib reduces proteinuria and relieves renal injuries in lupus MRL/lpr mice.This protective effect might be explained by its immunosuppressive action,which leads to reduced expression of TGF-β_1 and COX2 in the kidney of MRL/lpr mice,decreases the deposition of extracellular matrix.Specific COX-2 inhibitor has a renoprotective effect on MRL-lpr/lpr mice.