Abstract: Ducks were experimentally inoculated with a highly pathogenic avian influenza virus, A/duck/Guangdong/220/2004(H5N1) by intravenous and eyes-nares-mouth-cloaca routes, then the micro and ultrapathology were investigated. The pathologic lesions characterized by systemic hyperemia, congestions, hemorrhages, thrombosis, edema were observed in multiple organs; And the necrosis and apoptosis occurred in the heart, liver, spleen, lung, kidney, pancreas, encephalon, thymus and bursa of Fabricius etc. The most prominent lesions were vasculitis, necrotic pancreatitis, atrophic and necrotic thymusitis and bursatitis, splenitis, tracheitis, hemorrhagic bronchointerstitial pneumonia, viral myocarditis, nonsuppurative encephalitis, local viral hepatitis, ulcerous enteritis, tubulointerstitial nephritis and mesangial proliferatial nephritis. It was suggested that the pathogenic mechanism of the virus is involved in necrosis and apoptosis, and the severe pathologic lesions in multiple organs result in duck death.