The effects of the water extracts of Millettia reticulata Benth (WEMRB) and its active compound (protocatechuic acid [PCA]) on acute hepatic injury and inflammation in CCl(4)-induced Sprague-Dawley rats were investigated. Sprague-Dawley rats were orally treated with WEMRB or PCA for 28 consecutive days, and then the rats were given an intraperitoneal injection with CCl(4). Pretreatment with WEMRB or PCA significantly lowered the CCl(4)-induced serum levels of hepatic enzyme markers (aspartate and alanine aminotransferases). Liver histopathology showed that WEMRB reduced the incidence of cytoplasmic vacuolization and necrosis induced by CCl(4) in rats. Pretreatment with WEMRB also showed anti-inflammation on the expression of cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase, as well as nitrite and nitrate levels in the CCl(4)-induced Sprague-Dawley rats. The results suggest that oral administration of WEMRB decreases the hepatotoxic effects by increasing glutathione-dependent antioxidant enzyme activity, thereby reducing oxidative stress and inflammation in CCl(4)-induced Sprague-Dawley rats.