Impaired glomerular endothelial integrity is pivotal in various renal diseases and depends on both the degree of glomerular endothelial injury and the effectiveness of glomerular endothelial repair. Glomerular endothelial repair is in part mediated by bone-marrow derived endothelial progenitor cells (EPC). PPAR- agonists have therapeutic actions independent of their insulin sensitizing effects, including enhancement of EPC function and differentiation. We evaluated the effect of PPAR--agonist rosiglitazone (4 mg/kg/day) on the course of anti-Thy1-glomerulonephritis in rats. Rosiglitazone limited the development of proteinuria and prevented plasma urea elevation (8.1±0.4 vs. 12.5±1.1 mmol/l, p=0.002). Histologically, inflammatory cell influx was not affected, but rosiglitazone-treated rats did show fewer microaneurysmatic glomeruli on day 7 (26±3 vs. 41±5%, p=0.01) and reduced activation of matrix production with reduced renal cortical TGF-, PAI-1 and Fibronectin-1 mRNA expression. However, bone marrow derived endothelial cell glomerular incorporation was not enhanced (3.1±0.4 vs. 3.6±0.3 cells per glomerular cross section; p=0.31). Rosiglitazone treatment in non-nephritic rats did not influence proteinuria, urea or renal histology. In conclusion, treatment with PPAR--agonist rosiglitazone ameliorates the course of experimental glomerulonephritis in a non-diabetic model, but not through enhancing incorporation of bone marrow-derived endothelial cells in the glomerulus.