Acute renal failure (ARF) results in significant morbidity and mortality, yet renal failure itself is not the usual cause of death in the clinical situation. Recent studies have suggested that damages to the kidneys cause liver tissue alterations. Thus, the death may be related to liver complications as well as renal injury. The aim of the present study was to assess the hepatic changes during various periods of reperfusion after induction of renal ischemia. Forty male rats were subjected to either sham operation or 45 min ischemia followed by 1, 3, 6, and 24 hours of reperfusion. Arterial blood pressure was continuously monitored. Blood samples were drawn post-operatively to measure serum creatinine and BUN. Hepatic concentrations of IL-10 and tumor necrosis factor TNF)-α were evaluated. A portion of liver and kidney tissues were fixed for histological evaluations. Reperfusion caused significant changes in liver structure and a significant reduction in renal function demonstrated by increase in serum creatinine and BUN. These rats also showed a significant increase in hepatic TNF-α and IL-10 concentrations. Most changes observed in 3 hrs reperfusion (e.g. TNF-α, 616±41 vs 215±16 and IL-10, 926±73 vs 125±34, pg/100 mg tissue, p≤0.05). Renal ischemia-reperfusion results in distant effects on liver histology, function and inflammatory status. These may have been due to increased renal production or impaired clearance of mediators of tissue injury, such as pro-inflammatory cytokines. The reduction in liver injury in 24 hrs reperfusion comparing to the other groups, suggests activation of late-protective mechanisms. These observations may be important in the clinical interventions to reduce the morbidity and mortality of ARF.