Acute kidney injury is a common complication of myocardial infarction (MI) and scarce data were available on the effect of vitamin D3 on heart and kidney functions in MI. In this study, we investigated the potential protective effect of vitamin D3 on cardiorenal functions in isoproterenol-induced MI in rats and the possible mechanisms involved. It was shown that in MI rats, there was a significant increase in serum levels of (creatine kinase myoglobin binding, lactate dehydrogenase, creatinine, malondialdehyde, interlukin-6 and tumor necrosis factor alpha) and urine levels of (total protein and albumin), with a significant decrease in urine creatinine level, creatinine clearance and serum levels of [reduced glutathione and 1, 25 dihydroxy vitamin D] in comparison with the control rats. On treatment of rats with vitamin D3 prior to induction of MI, these changes were significantly improved in comparison with the MI rats. Histopathological and immunohistochemical examinations of heart and kidney in MI rats reflected the deterioration in their structures with presence of marked apoptosis which were ameliorated on treatment of rats with vitamin D3 prior to induction of MI. In conclusion, vitamin D3 has a protective effect on heart and kidney functions in the rat model of myocardial infarction and this beneficial effect could be related to its anti-inflammatory, antioxidant and anti-apoptoticactions.