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.