Progressive mesangioproliferative glomerulonephritis, mostly IgA nephropathy, is a major cause of end-stage kidney disease worldwide. In a chronic-progressive model of mesangioproliferative glomerulosclerosis (GS), we tested the renoprotective efficacy of rosuvastatin alone and in combination with a high-dose of the AT1 blocker candesartan. Treatment was started one week after disease induction (anti-thy1 antibody injection into uni-nephrectomized rats) and continued until week 20. Tubulointerstitial expression of the key fibrosis mediator TGF-B served as the main marker of disease progression. Compared to the untreated GS rats (475±52 pg/mL), tubulointerstitial TGF-B1 protein expression was significantly reduced by both single therapies (rosuvastatin -47%, candesartan -51%, p<0.01). Tubulointerstitial matrix accumulation (matrix score in GS: 64±7%) was reduced by -45% and -52%, respectively (p<0.01). The combination of rosuvastatin and candesartan had significantly greater effects on tubulointerstitial TGF-B1 expression (-82% vs. GS) and matrix accumulation (-83% vs. GS) (p<0.001 vs. GS, p<0.05 vs. single therapy) than either drug alone. Similar additive beneficial effects were observed for renal fibronectin and TIMP1 expression, cell proliferation, macrophage infiltration, proteinuria and kidney function. In conclusion, rosuvastatin limits the progressive course of anti-thy1-induced glomerulosclerosis towards chronic tubulointerstitial fibrosis and renal insufficiency to a degree comparable to the one achieved by a high dose of the AT1 antagonist candesartan. Combined treatment yields significantly greater actions on renal TGF-B overexpression and matrix accumulation, cell proliferation and macrophage infiltration. The results suggest that rosuvastatin and an AT1 blocker independently interfere with separate key pathways involved in the progression of chronic mesangioproliferative glomerulosclerosis.