Background: One striking feature observed during renal ischemia reperfusion injury (IRI) is the increase in interstitial fluid and infiltration, which reflects an increase in vascular permeability. Angiopoietin-1 (Ang-1) prevents vascular leakage and inflammation. Hyaluronic acid (HA) has a high capacity to bind and retain water and is pro-inflammatory factor. Material and Method: The authors evaluated the expression of Ang-1 and HA during renal IRI bilaterally for 30 minutes. Renal tissue was sent for pathologic study, proteins expression, and mRNA in renal IRI at 24 and 48 hr. Results: At 24 hr post-injury, histopathology studies revealed severe tubular epithelial cell (TEC) necrosis, peritubular capillary (PTC) congestion, mild interstitial infiltration, and edema. Histopathology at 48 hr post-injury showed a progressive increased degree of PTC congestion, interstitial infiltration and edema. In normal kidney, Ang-1 was abundant in glomerulus and PTC patterns, while HA is absent in the cortex but present in the medulla. At 24 and 48 hr post-IRI, kidney cortex and medulla showed a reduced Ang-1 staining but with an increase in HA staining. Western blot analysis showed that levels of Ang-1 expression decreased to 44% of normal levels at 24 hr post-IRI and further declined to 31% at 48 hr post-IRI. Using real time RTPCR, Ang-1 expression declined to 15% of normal levels at 24 hr post-IRI and sustained at 48 hr post-IRI. Conclusion: These results suggest that lowered Ang-1 expression levels and increased HA may contribute to an increased permeability and inflammation of microcirculation in renal IRI.