OBJECTIVE： To investigate the effects of total paeony glycoside （TPG） on the expression of tumor suppressor gene in lung cancer model rats. METHODS： 90 rats were randomly divided into normal group， model group， positive control group [cyclophosphamide， 50 mg/（kg·d）] and TPG low-dose， medium-dose and high-dose groups [50， 100， 200 mg/（kg·d）] with 15 rates in each group. Except for normal group， other groups were given disposable infusion of carcinogenic iodized oil via left lobe bronchus to induce lung cancer model. After modeling， those groups were given relevant medicine intravenously from Monday to Friday， while normal group and model group were given constant volume of normal saline intravenously for consecutive 16 weeks. The expression of multidrug resistance associated protein （MRP）， human multidrug resistance gene （MDR1）， P21 and P16 mRNA in lung tissue of rats were determined by RT-PCR； the expression of P53 protein in lung cancer tissue was determined by IHC method.The rate of positive expression was calculated， and pathological change of lung tissue was observed. RESULTS： Compared with normal group， the expression of MRP， MDR1， P21， P16 mRNA and P53 protein （positive rate of 66.67％） in lung tissue was increased significantly in model group （P＜0.05）； compared with model group， the expression of MRP， MDR1， P21， P16 mRNA and P53 protein （positive rate of 46.67％， 46.67％， 40.00％， 13.33％） decreased in positive control group， TPG low-dose， medium-dose and high-dose groups in dose-dependent manner， and the decrease of TPG medium-dose and high-dose groups were more significant than that of positive control group （P＜0.05）； there was statistical significance in above indexes among TPG groups （P＜0.05）. CONCLUSIONS： TPG could inhibit the expression of MRP， MDR1， P21， P16 gene and P53 protein in lung cancer model rats significantly.