Abstract: In this study, yellow catfish (Pelteobagrus fulvidraco) were infected by immersion challenge with Vibrio mimicus (1.0×10⁶ CFU · mL^-1).The challenged fish were sampled at 0, 4^th, 8^th, 16^th, 24^th, 36^th, 48^th, 60^th and 72^nd hour post infection to detect the histopathological changes and distribution of bacteria. Pathologic results show that skin, muscle, gills and intestines were the first to produce pathologic changes, and skin and muscle were most seriously damaged. Degeneration of the epidermis, edema of gill epithelium and intestinal mucous membrane were observed at 16^th hour post infection. Then, necrosis and fallen off of epidermis, serious hemorrhage of dermis and necrosis of muscle fibers, hemorrhage of gills and focal necrosis of intestines were observed from 24^th hour to 48^th hour; during 48^th hour to 72^nd hour, skin and muscle fibers formed ulcer lesions and gills showed hemorrhages and focal necrosis. Besides, liver, spleen, kidney and heart showed different degrees of pathological changes after 36-hour post infection, including congestion, hemorrhage, degeneration and focal necrosis. Real-time PCR results show that V.mimicus is were detected in gills, intestines and muscle initially at 4^th hour post infection and the quantity of bacteria were 1.3×10²CFU · mg^﹣1 in intestines, 2.6×10²CFU · mg^-1 in gills and 4.7×10²CFU · mg^-1 in muscle, respectively. The quantity of bacterial in gills and muscle increased at the rest of time and then reached a peak at 72^nd hour, about 4.7×10⁷CFU · mg^-1; After 24 h, V.mimicus is were detected in liver, spleen and heart, and the range of quantity was from 1.9×10 CFU · mg^-1 to 4.7×10²CFU · mg^-1. Results suggest that gill, intestine, muscle are first invasion sites of V.mimicus, and most of the internal organs can be invaded.