The freshwater clam is a widely-consumed shellfish and is used as a remedy for chronic hepatitis in Asia. However, its contribution to acute liver injury (ALI) remains unclear. The aim of this study is to assess the protective effects of freshwater clam extract (CE) in ALI induced by hemorrhage in rats. Rats were randomly divided into 5 groups, (1) blood loss (BL) 40%, (2) CE 150 mg/kg plus BL 40%, (3) CE 75 mg/kg plus BL 40%, (4) CE 150 mg/kg, and (5) CE 75 mg/kg groups. CE was given by femoral vein catheter in Groups 2 to 5. Initial hemorrhage was induced by withdrawing blood (loss 40% of total blood volume) from a femoral arterial catheter after CE administration in Groups 2 and 3. The levels of blood tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured at several time points during the experimental period. Rats were sacrificed after 48 hours, and the liver was harvested for hematoxylin and eosin (HE) stain to show liver tissue injury. The results indicated that hemorrhage significantly decreased mean arterial pressure (MAP), increased blood AST, ALT and LDH levels and induced liver injury. Pre-treatment with the CE increased MAP and IL-10 levels and decreased AST, ALT, LDH and TNF-α levels after hemorrhage. The HE stains showed diminished organ injury in the CE groups. In conclusion, freshwater clam extract is a potential immunomodulating agent and ameliorates acute liver injury.