Objective To investigate the etiology and pathologic features of two cases of hemorrhagic ulcer happened on channel catfish (Ietalurus punetaus).Method The gill tissue and body mucus were compressed by wet film method to detect potential parasite. Pathogen isolation was conducted using liver, spleen and kidney of diseased fish to detect potential bacterial infection. The homogenate of liver, spleen and kidney from diseased fish was detected for the channel catfish virus (CCV) by PCR. The pathologic features of diseased fish were observed by histopathology, and the causes of this disease were analyzed comprehensively.Result The spleen, kidney, hepatopancreas, intestine, skin and muscle were the main target organs of hemorrhagic ulcer. The main syndrome was severe vascular response with degeneration and necrosis of the parenchymal cells. Stomach, brain and heart had minor damages with slight inflammation, and gill filaments, eyeballs and swim bladder did not have obvious pathological changes. The diseased individuals displayed moderate to severe hemorrhagic necrotic spleen inflammation, moderate nephritis, and mild to moderate necrotic hepatopancreatitis and necrotic enteritis. No parasite, bacteria, or CCV was detected in diseased catfish.Conclusion Based on the results of pathological, bacteriological and virological examinations, it is inferred that the fulminant disease of catfish was caused by some non-CCV virus infection, and temperature stress may be the conditional incentive of this disease.