Abstract: An epidemic disease consecutively happened in cage - cultured channel catfish (Ictalurus punctatus) was recorded in Guangxi during 2006 to 2007. The disease was widely spread with high infectious and lethal feature, exophthalmia, disorientation, unilateral eyes turbidity, and large systemic bleeding in later stage, often 30% to 100% mortality. We isolated seven representative bacterial strains named as CMS003 - CMS005, CM$009 - CMS012 from the diseased fish. The challenge test of these isolated bacteria showed highly pathogenic to the fish. The challenged fish presented the similar external signs to natural infected catfish, such as exophthalmia and disorientation. These seven isolates were identified as Streptococcus iniae by the conventional morphological, physiological and biochemical characteristics, specific PCR diagnosis and 16S rRNA phylogenetic evolution of gene sequence analysis method, indicating that Streptococcus iniae was the main pathogen of cage cultured channel catfish.