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The present study investigated the effects of combination of hyaluronic acid (HA) and Wharton Jelly-derived mesenchymal stem cells (WJ-MSCs) on renal ischemia/reperfusion (I/R) injury in rats. 120 male Sprague Dawley rats were divided into 5 equal groups; a) sham operated, b) I/R (45 min left renal ischemia), c) HA group (0.04-0.08 ml of HA, 2-3 injections on lateral aspect of left kidney just after renal ischemia, d) WJ-MSCs-treated group (as control with 1 ×10^6 MSCs suspended in 0.15 ml complete medium on lateral aspect of left kidney after ischemia time) and e) WJ-MSCs + HA group (as control with HA and WH-MSCs). WJ-MSCs group showed significant decrease in serum creatinine, urinary proteins and kidney morphology with significant increase in creatinine clearance (p< 0.05). Moreover, HA +WJ-MSCs group showed more significant decrease in serum creatinine, urinary proteins and kidney morphology with more significant increase in creatinine clearance than WJ-MSCs group (p<0.05). We concluded that HA potentiates the reno protective effect of WJ-MSCs against renal I/R injury probably by increasing its homing and pro inflammatory function in injured tissues and in culture cells whish demonstrate by gene expression of Follistatin (FST), by RT-PCR. FST levels were significantly higher in the cells pretreated with HA, compared to control cells. This effect appeared at 48 h and up to 14 days.Keywords: WJ-MSCs, renal ischemia/reperfusion, Hyaluronic acid, Follistatin.