Abstract: 【Objective】In order to investigate the acute toxicity and histological microstructure of o-cresol on muscle, gill, and liver tissues of adult zebrafish, and provide theoretical basis for the molecular mechanism of the toxic effect of ocresol on zebrafish, environmental safety assessment and ecological risk assessment. 【Method】Adult zebrafish were divided into 6 groups and exposed to 0(control), 15.00, 19.74, 25.98, 34.19 and 45.00 mg/L o-cresol solution for 96 h using the static water method, respectively. The symptoms and numbers of death of poisoning of zebrafish in each group at 24, 48, 72 and 96 h were recorded. The mortality, median lethal concentration(LC₅₀)and the safe concentration(SC) were calculated, and the safety level was evaluated. The effects of different concentrations of o-cresol on the histological structure of muscle, gill and liver tissues of adult zebrafish were further analyzed based on histopathological techniques.【Result】Compared with the control group, the acute poisoning symptoms of zebrafish in the 45.00 mg/L(the highest concentration) group were characterized by difficulty breathing, wild swimming, convulsions, slight rolling, slow response to peripheral stimulation, and gradually losing balance and lying at the bottom of the water, all of which died within 24 h.The LC₅₀ of o-cresol on adult zebrafish at 24, 48, 72 and 96 h were 34.721, 30.079, 27.123 and 27.092 mg/L, respectively, and the safe concentration of o-cresol was 6.612 mg/L, which belonged to low toxicity compound. Histopathological analysis showed that the microstructure of muscle, gill and liver of zebrafish did not change significantly after 96 h of exposure at concentrations of 15.00 and 19.74 mg/L. However, when the concentration of o-cresol was 34.19 and 45.00mg/L, muscle fibers gradually broke, and swelling and necrosis appeared. In gill tissue,the end of the secondary lamellae was swollen and bleeding, the epithelial cells were swollen, shed and damaged, the number of red blood cells increased greatly, and the arrangement of various cells was disorderly. Large area vacuolation occurred in hepatocytes, hepatic nuclei atrophied, deformed, dissolved or migrated, and hepatocytes showed necrosis. 【Conclusion】The toxic effect of ocresol on adult zebrafish is enhanced with increasing exposure concentration and prolonged time, and which belongs to low toxicity phenolic pollutant. Exposure to high concentrations of o-cresol can cause severe damage to the microstructure of muscle, gill and liver tissues in adult zebrafish.