To study the acute toxicity and liver and kidney toxicity of raw Zhizi（Gardeniae Fructus）and six water extractswith different processing degrees using zebrafish model and explore the effect of processing degree on Zhizi（Gardeniae Fructus）toxicity.

Acute toxicity studieswere carried outon AB series zebrafish with normal development 3 days（3 dpf）after fertilization，and 6 different dose concentrationswere set for raw products（sp）and sixwater extractswith different degrees of preparation（pz1，pz2，pz3，pz4，pz5，pz6）. Themortality rate of zebrafish at72 h was statistically calculated. Quantitation-toxicity curveswere created using GraphPad Prism 9.0 software to calculate half lethal concentration（LC₅₀）and 10% lethal concentration（LC₁₀）. Liver and kidney injury studies were conducted on gz15Tg/+（AB）liver fluorescent protein transgenic zebrafish with normal development4 days（4 dpf）after fertilization. Three dose concentration groups were set up as low（LC₀），medium（LC₁₀）and high（LC₂₀）groups，and the acetaminophen group was setup，with embryonic water as the blank group. After72 h of administration，zebrafish livermorphology and fluorescence area changes were observed，and the activities of alanine aminotransferase（ALT）and aspartate aminotransferase（AST），creatinine（Cr）and urea nitrogen（BUN）were detected.

The results of acute toxicity experiments showed that the values of LC₅₀ of the raw productand six water extractswith different processing degreeswere 0.042，0.049，0.053，0.064，0.050，0.058 g·L^-1 respectively. The values of LC₁₀ were 0.024，0.025，0.033，0.038，0.036，0.036，0.039 g·L^-1 respectively. The results of liver and kidney injury showed that compared with those in the blank group，the livermorphological deformation and fluorescence area of zebrafish in the acetaminophen group decreased（P<0.01）and the activities of ALT and AST increased（P<0.01），indicating that acetaminophen was hepatotoxic to zebrafish. The livermorphological changes and fluorescence area of zebrafish in the low，medium and high groups of sp decreased（P<0.01），the activities of ALT and AST increased（P<0.01，P<0.05）and the activities of BUN and Cr rised（P<0.05），indicating the raw product had hepatic and renal toxicity to zebrafish. Livermorphology and fluorescence area of zebrafish decreased in themedium and high dose groups of pz 1，pz 2 and pz 3（P<0.01），the activities of ALT and AST in pz1 group increased（P<0.01），the activities of BUN and Cr elevated（P<0.01，P<0.05），the activity of ALT in the low，medium and high dose groups of pz2 and pz3 rised（P<0.05，P<0.01），and the activities of AST in themedium and high dose groups increased（P<0.05，P<0.01）. There were no significant changes of livermorphology or fluorescence area in the low and medium dose groups of pz4，pz5 and pz6，and there were changes in the high dose group（P<0.05）. The results showed that the low and medium dose groups of pz4，pz5 and pz6 had no significant effect on the liver of zebrafish，and there was liver damage in the high dose group. ALT and AST were elevated in themedium and high dose groups of pz4（P<0.05，P<0.01）. There was no significant effect on the decrease in the activity of ALT of pz5 and pz6 and there was liver injury in the AST high dose group（P<0.01，P<0.05）. The activities of BUN and Cr were increased in the high dose groups of pz3 and pz5（P<0.01，P<0.05），and the activitieswere elevated in the high dose group of pz4（P<0.01）. The results showed that sp and pz1～pz5 had different degrees of damage to the liver and kidney of zebrafish with different degrees of preparation and different doses. There was no liver or kidney injury neither in the three dose concentration groups of pz6 nor in the ALT，BUN，Cr and AST low and medium dose groups of zebrafish.

The liver and kidney injury of Zhizi（Gardeniae Fructus）is related to the degree of processing and dosage. But raw and different processing degrees products showed certain liver and kidney damage to varying degrees. Standardizing the processing conditionsmay be an importantmeasure to realize themedication safety of gardenia.