Korea had experienced second epidemic highly pathogenic avian influenza (HPAI), and there were the seven affected farms, including two breeder duck farms, from 22nd November 2006 to 6th March 2007. Here, we reported the clinico-pathological characteristics of domestic breeder ducks farms naturally infected with HPAI virus (H5N1). Clinically, the most ducks showed various signs from depression, decreased egg production and feed consumption to even, death. The most commonly gross changes were hepatomegaly, splenomegaly, petechial and ecchymotic hemorrhage on the liver surface, a white stripe on the cardiac muscle, and severely hemorrhagic and deformed eggs. The most significant histopathological changes were necrosis of various cells such as neuron, lymphocytes, cardiac myocytes, hepatocytes, blood vessels and pancreatic acinar epithelium. The viral antigen was mainly detected in the endothelium of blood vessels of various organs and tissues, peripheral nerves and neuronal cells. Based on the above results, we identified that HPAI H5N1 induced systemic infection in the adult breeder ducks.