Endothelial cells (ECs) are highly susceptible to hypoxia and easily affected upon ischemia/reperfusion (I/R) during renal transplantation. Pericytes and angiopoeitins play important roles in modulating EC function. In the present study, we investigate the effect of renal I/R on dynamics of angiopoietin expression and its association with pericytes and fibrosis development. Male Lewis rats were subjected to unilateral renal ischemia for 45 minutes followed by removal of the contralateral kidney. Rats were sacrificed at different time points after reperfusion. Endothelial integrity (RECA-1),pericytes (PDGFRβ), Angiopoietin-2 (Ang-2)/Angiopoietin-1 (Ang-1) expression and interstitial collagen deposition (Sirius Red and α-SMA) were assessed using immunohistochemistry and RT-PCR. Our study shows an increase in protein expression of Ang-2 starting at 5 hours and remaining elevated up to 72 hours, with consequently higher Ang-2/Ang-1 ratio after renal I/R (p<0.05 at 48 hours). This was accompanied by an increase in protein expression of the pericytic marker PDGFRβ and a loss of ECs (both at 72 hours after I/R, p<0.05). Nine weeks after I/R, when renal function was restored, we observed normalization of the Ang-2/Ang-1 ratio and PDGFRβ expression and increase in cortical ECs, which was accompanied by fibrosis. Renal I/R induces a dysbalance of Ang-2/Ang-1 accompanied by proliferation of pericytes, EC loss and development of fibrosis. The Ang-2/Ang-1 balance was reversed to baseline at 9 weeks after renal I/R, which coincided with restoration of cortical ECs and pericytes. Our findings suggest that angiopoietins and pericytes play an important role in renal microvascular remodeling and development of fibrosis.