Objective To study the preventive effect and mechanism of Rhubarb extract on renal injury after cardiopulmonary resuscitation (CPR) in rabbits with cardiac arrest (CA).Methods Twenty-four male Japanese big-ear rabbits were divided into sham operation group, CPR model group and Rhubarb pretreatment group by random number table method, with 8 rabbits in each group. The rabbits in Rhubarb pretreatment group were treated with Rhubarb extract 5 mL·kg-1·d-1 for 7 days; and those in sham operation group and CPR model group were fed with 0.9％ normal saline 10 mL/d for 7 days. After 7 days, ventricular fibrillation (VF) was produced in CPR model group and Rhubarb pretreatment group by 50 V alternating currents stimulation through bottom of the heart leads to the apex to prepare CPR model. The rabbits of the CPR model group and Rhubarb pretreatment group were sacrificed at 2 hours after successful resuscitation, and the animals in the sham operated group were sacrificed directly after anesthesia. The levers of blood urea nitrogen (BUN) and creatinine (Cr) in serum were examined by automatic biochemical analyzer. The positive expression area of neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in kidney were examined by immunohistochemistry.Results Compared with the sham operation group, the levels of BUN and Cr were significantly increased in the CPR model group and Rhubarb pretreatment group [BUN (mmol/L):15.53±3.90, 10.51±3.16 vs. 7.03±2.23, Cr (μmol/L): 137.20±12.23, 86.80±7.67 vs. 66.39±5.47, bothP < 0.05]. Compared with the CPR model group, the levels of BUN and Cr were significantly decreased in the Rhubarb pretreatment group [BUN (mmol/L): 10.51±3.16 vs. 15.53±3.90, Cr (μmol/L): 86.80±7.67 vs. 137.20±12.23, bothP < 0.05]. Immunohistochemical staining showed that the expression of NGAL and IL-18 mainly existed in glomerular and tubular cells in patina. Compared with the sham operation group, the positive expression areas of NGAL and IL-18 in kidney were significantly increased in the CPR model group and Rhubarb pretreatment group [NGAL (μm2): 208.26±7.58, 136.74±5.33 vs. 98.93±7.83, IL-18 (μm2): 256.48±4.64, 113.22±6.98 vs. 77.06±6.47, allP < 0.05]. Compared with the CPR model group, the positive expression areas of NGAL and IL-18 were significantly decreased in the Rhubarb pretreatment group [NGAL (μm2): 136.74±5.33 vs. 208.26±7.58, IL-18 (μm2): 113.22±6.98 vs. 256.48±4.64,bothP < 0.05].Conclusions CA can lead to acute kidney injury (AKI). Rhubarb extract can reduce the expression of NGAL and IL-18 in kidney of rabbits after CPR, and protect the kidney after CPR.