Abstract: 【Objective】In order to evaluate the acute toxicity of fenvalerate, phoxim, sulfide gatifloxacin and ridomil to Procambarus clarkii, analyze the histopathological effects on P. clarkii, and provide basic data for ecological risk assessment.【Method】The acute toxicity effects of four drugs on P. clarkii were determined by static test method. P. clarkii were soaked in four drugs for 48 and 96 h with 10% concentration of 48 h half lethal concentration(LC₅₀) and 10% concentration of 96 h-LC₅₀ respectively. The changes of hepatopancreas and muscle structure of P. clarkii were compared and analyzed based on paraffin section technology.【Result】The poisoning symptoms of the four drugs were similar, and the poisoning symptoms of different concentration groups showed obvious dose and time effects. The results of acute toxicity test showed that, toxicity ranking of four chemical drugs was fenvalerate>phoxim>sulfide gatifloxacin>ridomil. The LC₅₀ of fenvalerate to P. clarkii was 4.375, 4.252 and 3.865 μg/L at 24, 48 and 96 h. The LC₅₀ of phoxim to P. clarkii was 161.301, 87.784 and 81.637 μg/L. 24, 48 and 96 h-LC₅₀ of sulfide gatifloxacin to P. clarkii was 76.541, 72.509 and 52.529 mg/L. And the LC₅₀ of ridomil for P. clarkii at 24, 48 and 96 h respectively were 20.610, 5.499 and 4.141 g/L. Histopathological observation showed that the tissues of P. clarkii were still damaged and destroyed after being exposed to relatively low concentrations of chemical drugs. The results showed that part of hepatopancreas cells ruptured, shrunk and necrosis, the volume of B cells and its internal transport vesicles increased greatly, and the color of R cells deepened;the whole muscle showed the phenomenon of breaking and dissolving of muscle fibers, loose arrangement of cells and obvious cavity.【Conclusion】The acute toxicity of fenvalerate, phoxim, sulfide gatifloxacin and ridomil to P. clarkii is different.P. clarkii can survive at the safe concentration of four chemicals, but it damages the hepatopancreas and muscle tissue.