Background: Autophagy means bulk degradation and recycling of cytoplasmic constituents to maintain cellular homeostasis. In response to stress, autophagy is induced and may contribute to serve as a cell survival mechanism. Very little is known about autophagy in renal pathophysiology. Aim of the study; the aim of the present study is to examine autophagy activator metformin and its role in renal cell injury using models of ischemia−reperfusion. Methods; Sham rats (control, n = 10); the rats in the sham group underwent laparotomy under anesthesia without any treatment, Group 2 (Ischemic-reperfusion injury, I/R,n =20); bilateral renal pedicles were clipped for 45 min, followed by perfusion for 24 h to establish I/R model, Group 3(IR + metformin 300 mg/kg , n = 20), Animals were pretreated with the metformin (Met) at 300 mg/kg 2 does 2h, 12h prior to 45 min of ischemia. Results: the effect of I/R of the kidney on the renal cells resulted in disturbed renal function as evidenced by the increase in kidney Function tests parameters and protective effect of metformin on renal cells that was evaluated by assessment of urea, creatinine, MDA. conclusion: The results suggested the protective effects of metformin on induced autophagy ameliorating the I/R injury of the kidney.