Objective: The effect of matrix metalloproteinase (MMP) inhibitors in segmental sclerosis is unknown. The aim of this study is to investigate the effect of a MMP inhibitor, doxycycline, on glomerulosclerosis (GS) in renal ablation nephropathy. Method: Fourteen of the 32 female Wistar albinos were 5/6 nephrectomised. Doxycyline was given to half of each group (40 mg/kg/day total 28 days). After sacrification, the GS, MMP-2, MMP-9, TIMP-2 expressions were analyzed histopathologically. Pro and active MMP-2 and -9 were analyzed by gelatin zymography. TIMP-1 and TIMP-2 were measured with ELISA assay. Results: Doxycycline administration to the 5/6 nephrectomy group improved GS, but did not inhibit glomerular MMP-9 or cortical pro-and active-MMP-2 and pro-MMP9 but increased TIMP-1 and TIMP-2 expression in all groups in cortical tissue. MMP-9 expression and GS were increased in all groups receiving doxycycline. Conclusion: We have demonstrated improved GS in renal ablation model by doxycycline administration but also doxycycline has an unexpected adverse effect. The effect of doxycycline on the expression of MMP-2 and -9 cannot explain the improvement in GS, but increased cortical TIPM-1 and -2 may be an important contributing factor for inhibition of MMPs.