Abstract: Skin ulceration syndrome (SUS) is the most devastating disease affecting the aquaculture of the Japanese sea cucumber (Apostichopus japonicus), with multiple bacterial pathogens implicated in its occurrence. In this study, pathogens were isolated and purified with the plate isolation method from the Japanese sea cucumber affected by SUS collected from aquaculture area of Xiapu, Fujian Province, in 2023. Species identification used a multi-method approach, integrating morphological, physiological, biochemical, and molecular biological analyses. Genomic sequencing and drug susceptibility testing were performed on the isolated pathogenic strain. Results revealed a dominant strain, FT2-H, isolated from the body surface lesions of the infected Japanese sea cucumbers. Based on its morphological characteristics, physiological and biochemical traits, and 16S rRNA gene sequencing, the strain was identified as Vibrio cyclitrophicus. Reinfection experiments confirmed the significant pathogenicity of FT2-H of the Japanese sea cucumber. Histopathological analysis showed that damage specifically localized to the body wall tissues, characterized by pathological dissolution of the cuticle and epidermis, while no lesions were observed in the intestine, respiratory tree, or other internal tissues. Genomic sequencing indicated that strain FT2-H annotated 178 gene fragments in the Virulence Factors Database (VFDB), corresponding to 77 virulence genes, including mannose-sensitive hemagglutinin gene (mshA), hemolysin gene (AHML_18530), type II secretion pathway gene (epsL), chemotaxis protein gene (cheA), and type IV pilus-associated gene (pilQ). The findings demonstrate that strain FT2-H carries multiple pathogenic factors capable of causing tissue dissolution and damage in the body wall of the animals, leading to SUS. Drug susceptibility tests showed that strain FT2-H exhibited high sensitivity to 15 antibiotics, including trimethoprim-sulfamethoxazole, ciprofloxacin, ampicillin, and ceftriaxone. These results provide a scientific basis for disease prevention and healthy aquaculture practices of the Japanese sea cucumber.