Objective,2,To investigate the mechanism of Tangluoning for alleviating pyrodeath of sciatic nerve cells in KK-Ay diabetic mice by SIRT1.,Methods,2,Ten SPF male C57BL/6J mice aged 8 weeks with ordinary feed were selected as blank control group and 30 SPF male KK-Ay mice aged 8 weeks were fed with high fat diet for 4 weeks. Random blood glucose ≥16.7mmol/L was detected as diabetic mouse model was successfully established.The successfully modeled mice were randomly divided into three groups：model group，low-dose Tangluoning group and high-dose Tangluoning group.The low-dose Tangluoning group was given intragastric administration of crude drug 10g/（kg•d），the high-dose Tangluoning group was given intragastric administration of crude drug 20g/（kg•d），the blank control group and the model group were given intragastric administration of equal volume distilled water， free diet during the experiment， continuous administration for 12 weeks.The morphological structure of sciatic nerve cells was observed by transmission electron microscopy，and the expression levels of SIRT1 and scorched-death related molecules （Caspase1， NLRP3， GSDMD） were detected by Western blot.,Results,2,Compared with the blank control group， the expression level of SIRT1 protein in model group was significantly down-regulated（,P,<,0.05）， the protein expression levels of Caspase1， NLRP3 and GSDMD increased （,P,<,0.05）；compared with the model group， SIRT1 protein expression in Tangluoning high-dose group was significantly increased （,P,<,0.05），Caspase1， NLRP3 and GSDMD protein expression levels were decreased （,P,<,0.05）.,Conclusion,2,Tangluoning can reduce scorch death of sciatic nerve cells in DPN mice，and part of its mechanism may be realized through up-regulation of SIRT1， and the effect of high-dose Tangluoning is more obvious.