Renal ischemia/reperfusion injury (IRI) is a common clinical problem involving oxidative stress and gap junction protein defects. Abscisic acid (ABS), a phytohormone regulating physiological functions in plants against various stresses, has been identified in mammalian tissues, too. We aimed to assess the role of synthetic ABS in management of renal IRI in comparison or combined with Metformin and whether it can modulate the gap-junction protein; CX43, and the oxidative stress related factors; NOX4, MDA and GSH; and apoptosis markers; BAX, BCL2 and P53. Rats were assigned to five groups ;1, Saline: 2, I/R+Sal., 3 I/R+Metformin, 4, I/R +ABS and 5, I/R + Metformin + ABS. Serum creatinine and K+, mRNA for CX43, NOX4 and P53, western blotting for CX43 and P53 in renal tissue, immunohistochmistry for renal BAX and BCL2 with H&E and PAS staining were performed. Adminstration of Metformin, ABS or their combination led to a significant attenuation of the I/R induced renal injury with significant decrease in serum creatinine, K⁺ levels, and in the expression of P53, BAX, NOX-4 and caused a significant increase in CX43 and BCL2 expressions with attenuation of renal histopathological changes e.g. glomerular atrophy, tubular necrosis, tubular dilatation, sloughing of tubular epithelium, loss of brush border, cast formation and the inflammatory infiltration. Moreover, the combined therapy of Metformin and ABS produced more significant improvement. Our results approved a possible protective role of ABS especially when combined with Metformin in I/R renal injury