Abstract: Karenia mikimotoi, a frequently toxic and harmful bloom-forming species in China's coastal waters, could produce multi-toxins and cause considerable death of fishes or shellfishes when it blooms. The acute toxicity effects (72 h) of K. mikimotoi to fish Oryzias melastigma from cell biology, cell oxidation and immune enzyme activities have been studied and hence to find out how K. mikimotoi killed the fishes. Exposing to a high concentration of K. mikimotoi (1.37～1.52)×10⁷ cells/L, results of tissue sections in O. melastigma showed that gill filaments were broken and merged with nearby filaments as lumpy forms, positions shifting of epithelial cell nucleus for gills, and vacuolation occurred in liver cells. The high concentration of K. mikimotoi inhibited enzyme activities of superoxide dismutase (SOD) and catalase (CAT) in gill and liver cells and increased contents of malondialdehyde (MDA) for O. melastigma. It caused over-oxidation of cell membrane lipid and damage to tissue structure. Our results suggested that K. mikimotoi caused damage to gill and liver cellsof O. melastigma via oxidative stress, which provides an insight into the toxicity mechanism of K. mikimotoi.