Pleurotus ostreatus (PO), which is also called the oyster mushroom, is the secondly most popular cultivated mushroom in the world and has been shown to display antioxidant activity. In this study, the hepatic protective effects of extracts of PO cultured in wheat (POW) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats were evaluated by analyzing blood markers of liver injury. Sprague-Dawley rats were pretreated with POW extracts (0, 0.5, and 1.0 g/kg) orally for 14 days prior to the administration of $CCl_4$ for 3 days. Marked evaluation of alanine and aspartate aminotransferases, lactate dehydrogenase, alkaline phosphatase, and ${gamma}$-glutamyltransferase were observed in the plasma from control rats after $CCl_4$ treatment. This increased liver injury markers were significantly reduced in a dose-dependent manner by pretreatment with the POW extract, suggesting that POW prevented acute liver damage in $CCl_4$-intoxicated rats by suppressing cellular leakage and loss of the functional integrity of cell membranes in the liver. POW extracts could also improve lipid profiles damaged caused by $CCl_4$ in liver through a reducing plasma triglyceride and total cholesterol and a recovering plasma HDL-cholesterol. These results suggest that the extracts of POW ameliorate hepatotoxicity induced by $CCl_4$ in the rat model.