OBJECTIVE： To evaluate the DNA damage response of procarbazine hydrochloride （PCZ） and ethyl carbamate （EC） to different tissues in rats by performing alkaline comet assay， to validate the feasibility of alkaline comet assay of various tissues. METHODS： Totally 30 SD rats were randomly divided into 6 groups according to body weight， with 5 rats in each group， such as negative control group （hyperpure water）， PCZ 75 mg/kg group， PCZ 150 mg/kg group， EC 400 mg/kg group， EC 800 mg/kg group， positive control group （N-ethyl-N-nitrosourea 40 mg/kg）. Those rats were given relevant medicine intragasttrically for 4 d； clinical symptoms of rats were observed and body weight was recorded during experiment. Within 3 h after last medication， the rats were sacrificed； liver， renal and lung weight were weighed； liver， kidney， lung and peripheral blood lymphocytes were collected. The single cell suspension was prepared to perform alkaline comet assay. After lysis， unwind， electrophoresis and dying， tail DNA％ and tail distance of samples were analyzed by Komet 6.0 software. RESULTS： Compared with negative control group， body weight， liver and renal weight of rats were decreased significantly in PCZ 75 mg/kg group， PCZ 150 mg/kg group and positive control group 4 d after medication （P＜0.05 or P＜0.01）. Body weight of rats were decreased significantly in EC 800    mg/kg 4 d after medication （P＜0.05 or P＜0.01）； there was no statistical significance （P＞0.05）. Compared with negative control group， tail DNA％ and tail distance in liver， kidney and peripheral blood lymphocytes were increased significantly in PCZ 75    mg/kg group， PCZ 150 mg/kg group and positive control group （P＜0.05 or P＜0.01）； PCZ showed more significant effects on liver and lung. Tail DNA％ and tail distance of liver， kidney and peripheral blood lymphocytes were increased significantly in EC 800 mg/kg group （P＜0.05 or P＜0.01）， and tail DNA％ and tail distance of renal tissue was increased significantly in EC 400   mg/kg group （P＜0.05）. CONCLUSIONS： PCZ induced stronger DNA damage； liver and lung are the major genotoxicity target of PCZ. EC-induced DNA damage is relatively weak， and kidney is the most sensitive organ for EC-induced genotoxicity.