The toxicity and bioaccumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) continues to be a focus of research in human and various species. The main human exposure is via the dietary route. This study was carried out to investigate the protective effect of Cornu Cervi Parvum extract on clinical parameters and hepatotoxicity in Sprague-Dawley rat (SD rat) accutely exposured to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Male SD rats received single intraperitoneal (ip) injection of TCDD (40 ㎍/kg), and administered 10 or 20 mg/kg/day of the ethanol extract oral injection for 4 weeks from 1 week before TCDD treatment. The gain in body weight was less in group treated with TCDD than in CON group, while that of C/H+ TCDD group (Cornu Cervi Parvum extract 20 mg/kg/day) increased. The decrease in spleen and testis weight caused by TCDD was prevented by Cornu Cervi Parvum extract 20 mg/kg/day. The fluctuation in BUN content, WBC and platelet count by TCDD intoxication were significantly attenuated by the ethanol extract treatment (20 mg/kg/day for 4 weeks). Treatments of rats with the extract (10 or 20 mg/kg/day) were significantly reduced AST and ALT levels compared with TCDD-treated group. Moderate swelling of hepatocytes, hyperchromatism, acidophilic cytoplasm and cytoplasmic vacuolation were observed in TCDD-treated animals (TCDD group). The administration of EtOH extract 10 or 20 mg/kg along with TCDD significantly alleviated the liver histopathological alteration induced by TCDD. These results suggest that Cornu Cervi Parvum extract can be useful as a protective agent against TCDD, an endocrine disruptor.