Objective-: To investigate the role of recombinant human interleukin-11 (rhIL-11) on in vivo mobilization of CD34/vascular endothelial growth factor receptor (VEGFR) 2 mononuclear cells and collateral vessel remodeling in a mouse model of hindlimb ischemia. Methods and results-: We observed that treatment of Sv129 mice with continuous infusion of 200-μg/kg rhIL-11 per day led to in vivo mobilization of CD34/VEGFR2 cells that peaked at 72 hours. Sv129 mice pretreated with rhIL-11 for 72 hours before femoral artery ligation showed a 3-fold increase in plantar vessel perfusion, leading to faster blood flow recovery; and a 20-fold increase in circulating CD34/VEGFR2 cells after 8 days of rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4-fold influx of perivascular CD34/VEGFR2 cells after 8 days of therapy. Functionally, rhIL-11-treated mice showed better hindlimb appearance and use scores when compared with syngeneic mice treated with PBS under the same experimental conditions. Conclusion-: These novel findings show that rhIL-11 promotes in vivo mobilization of CD34/VEGFR2 mononuclear cells, enhances collateral vessel growth, and increases recovery of perfusion after femoral artery ligation. Thus, rhIL-11 has a promising role for development as an adjunctive treatment of patients with peripheral vascular disease. © 2011 American Heart Association, Inc.