Abstract A growing body of evidence suggests the contribution of aldosterone in induction of oxidative stress, endothelial dysfunction, inflammation and fibrosis in the vasculature, heart and kidney leading to progressive target organ damage. However, its role in liver injury is not clearly elucidated. The aim of this study is to investigate the effect of eplerenone, a selective mineralocorticoid receptor antagonist, on liver injury in rat and the possible underlying mechanisms. Liver injury was induced by intraperitoneal injection of thioacetamide (200 mg/kg body weight, 3 times per week for 4 weeks). Thioacetamide injection resulted in significant increase in serum aspartate aminotransferase, alanine aminotransferase, interleukin 6, Tumor necrosis factor alpha and hepatic malondialdehyde concomitant with significant decline in the indices of antioxidant capacity, hepatic reduced glutathione and superoxide dismutase. Treatment with eplerenone (4 mg/kg/day for 4 weeks) in thioacetamide injected rats significantly restored these values to nearly the control values. The present study suggests implication of aldosterone in the pathophysiology of liver injury as treatment with eplerenone has hepatoprotective effect against liver injury induced by thioacetamide via reducing liver enzymes, inflammatory markers and oxidative stress.