Abstract： Objective To study the preventive effects of rosiglitazone (RGZ) on chronic cyclosporine nephropathy (CCN) and the underlying mechanism.Methods Healthy male SD rats fed on LSD for one week were randomly assigned to normal group, RGZ (5 mg·kg-1 · d-1) group, cyclosporine A (15 mg·kg-1·d-1) group, RGZ treatment (cyclosporine A, 15 mg·kg-1·d-1 + RGZ, 5 mg·kg1·d-1) group after CAZN.Three rats in each group were sacrificed randomly 2 weeks later, and the rest were killed at the end of the experiment (5 weeks later).Serum creatine (Ccr) and albumin (ALB) were determined.Interstitial mononuclear cells were counted in HE staining, and interstitial fibrosis was calculated in Masson's staining.RT-PCR was used to detect the expression of MMP-9 and TIMP-1 in renal tissues of rats.Results Ccr in CsA-treated rats was decreased significantly (P<0.05), and RGZ ameliorated the decrease of Ccr markedly at the 5th week (P< 0.05).The serum level of AIB was decreased markedly in CsA-treated rats (P<0.05), but RGZ failed to improve the ALB neither at the 2nd nor at 5th week (P>0.05).The amount of interstitial mononuclear cells infiltrated was increased markedly in CsA-treated rats at the 2nd week (P>0.05).Tube atrophy, globule sclerosis and interstitial fibrosis were observed with Masson's staining in CsA-treated rats, progressed with time, and peeked at the 5th week.RGZ significantly alleviated fibrosis at the 5th week (P<0.05).In comparison with normal group, the expression of MMP-9 and TIMP-1 in CCN and treatment groups was markedly increased (P<0.05).In comparison with CCN group, the expression of MMP-9 and TIMP-1 was significantly decreased in treatment groups (P<0.05).Conclusion RGZ may alleviate chronic cyclosporine nephropathy by decreasing the expression of MMP-9 and TIMP-1.