The end-point of kidney injury is the development of fibrosis eventually leading to the development of chronic kidney disease (CKD)1. Due to the growing prevalence of CKD and the significant cost associated with treating end-stage renal disease in the form of dialysis or transplantation, it is imperative that novel, cellular based therapies, aimed at attenuating the progression of disease and promoting endogenous tissue repair, are explored. Mesenchymal stem cells (MSCs) can promote kidney repair in acute injury models through the release of mitogenic and angiogenic factors2. However, in the setting of chronic disease where fibrosis is established, the efficacy of MSCs is thought to be hampered. Here we tested the ability of MSCs in conjunction with the anti-fibrotic hormone, relaxin, to home to the kidney and induce repair in the kidney after 7 days of unilateral ureteric obstruction (UUO). Male C57BL/6 mice were allocated into sham and treatment groups (n=4-6) receiving vehicle (PBS), 1 x 106 MSC (i.v), or the combination of relaxin (subcutaneous osmotic pumps) and MSCs. Bioluminescence imaging confirmed that GFP/luciferase tagged MSCs were able to migrate to the UUO-injured kidney as early as one hour post cell delivery. The kidneys from UUO-injured mice receiving combination therapy had improved renal histopathology, resolved extracellular matrix expansion and a significant reduction in kidney injury molecule (Kim)-1 expression, compared to mice receiving MSCs alone. Additionally, combination therapy afforded enhanced protection by preventing fibrosis, as evident by a reduction in total kidney collagen concentration (hydroxyproline analysis) and interstitial collagen accumulation (picrosirius red-stained morphometry) and a significant increase in matrix metalloproteinase (MMP)-2 activity (gelatin zymography) (all p<0.05 vs. UUO+MSC treated group). These results demonstrate that the administration of relaxin improves MSC-induced repair and protection of the kidney from fibrotic injury.