To explore the mechanism of Colquhounia root tablets in inhibiting podocyte apoptosis of diabetic kidney disease(DKD).Methods:According to the random number table method，24 db/db mice were divided into the model group，Colquhounia root tablet group，and irbesartan group，with eight mice in each group，and 8 db/m mice as the control group.The Colquhounia root tablet group was given 280.83 mg/(kg·d) of Colquhounia root tablet suspension for gavage administration，while the irbesartan group was given 14.97 mg/(kg·d) of irbesartan suspension for administration.Meanwhile，the control group and model group received an equal volume of physiological saline for administration，with the course of treatment for eight weeks.The general condition，renal function，urinary protein，renal pathology，and the expression of Nephrin，SIRT1，Ac-p53，Caspase-3，Bcl-2 and Bax in mice were observed.Mouse podocyte cells 5 were divided into the control group，model group，Colquhounia root tablet group，Colquhounia root tablet+SIRT1 inhibitor group，and Colquhounia root tablet+EX527+p53 inhibitor group.The podocyte apoptosis and the expression of Nephrin，SIRT1，Ac-p53，Caspase-3，Bcl-2，and Bax proteins were detected.Results:Colquhounia root tablets can improve the general condition，renal function，urinary protein and renal pathological changes of DKD mice，increase the expression of Nephrin and SIRT1 in kidney tissue and podocytes，and decrease the expression of apoptosis factors(P<0.01).In the Colquhounia root tablet+EX527 group，the expression of Nephrin，SIRT1，and Bcl-2 proteins decreased(P<0.01 or P<0.05).In the Colquhounia root tablet+EX527+PFT-α group，the expression of Nephrin increased compared with the model group，and the expression of Ac-p53 and Caspase-3 proteins decreased compared to the model group and Colquhounia root tablet+EX527 group(P<0.01 or P<0.05).Conclusion:Colquhounia root tablets can block the podocyte apoptosis via the mitochondrial pathway by regulating SIRT1 deacetylation p53，and exert the protective effect of DKD on kidneys.