Angiostatin, a proteolytic fragment of plasminogen, is a potent anti-angiogenic factor recently shown to also have an inhibitory effect on leukocyte recruitment and macrophage migration. As both angiogenesis and inflammation play key roles in progression of chronic kidney disease, we evaluated the effect of angiostatin treatment in the rat remnant kidney model. Rats were pre-treated with recombinant adeno-associated viruses expressing either angiostatin or green fluorescence protein for four weeks. Chronic renal disease was then induced by a subtotal nephrectomy and rats sacrificed eight weeks later for analysis. Angiostatin treatment was associated with significantly less proteinuria, but no alterations in serum creatinine, creatinine clearance and blood urea nitrogen levels. Treatment with angiostatin reduced renal peritubular capillary number and decreased urinary nitric oxide levels. Despite reducing capillary density, angiostatin diminished interstitial fibrosis in association with reduced macrophage and T cell infiltration and renal MCP-1 mRNA levels. In conclusion, angiostatin overexpression was associated with attenuated renal disease progression in a model of chronic kidney injury, likely due to its anti-inflammatory actions. However, its anti-angiogenic actions suggest countering effects that could partially offset its benefit in chronic kidney diseases.