To explore the mechanism of action of Jianpi Yiqi Shexue Formula in treating fatigue in primary immune thrombocytopenia(ITP).Methods:A total of 90 BALB/c mice were divided into the following groups based on platelet(PLT) count:normal group,model group,prednisone group,Jianpi Yiqi Shexue Formula medium-dose group,and high-dose group,with 18 mice in each group.The PLT,weighted swimming time,and protein and mRNA expression of succinate dehydrogenase complex subunit A(SDHA),caseinolytic protease P(ClpP),Lon protease 1(LonP1) were compared among the groups.Results:Compared with the normal group,the model group had lower PLT,shorter weighted swimming time,and higher SDHA and ClpP protein and mRNA expression,while LonP1 protein and mRNA expression was lower(P<0.05).Compared with the model group,the Jianpi Yiqi Shexue Formula group showed higher PLT,longer weighted swimming time,and lower SDHA and ClpP protein and mRNA expression(P<0.05).The medium-dose Jianpi Yiqi Shexue formula group exhibited higher LonP1 protein expression(P<0.05),while the high-dose group showed higher LonP1 mRNA expression than the medium-dose group(P<0.05).Conclusion:The Jianpi Yiqi Shexue Formula can effectively increase PLT in ITP mice and alleviate fatigue symptoms.Its mechanism may involve regulating the expression of key mitochondrial proteases SDHA,ClpP,and LonP1,thereby restoring mitochondrial function.