Objective To explore the effects of Bufei Jianpi Formula (BJF) on mitochondrial damage of skeletal muscle in COPD rats by regulating IRS-1/PI3K signaling axis. Methods 60 SPF SD rats were randomly divided into blank group, model group (COPD stable stage group), BJF group, pioglitazone group (PIO group), BJF PIO group and aminophylline group, with 10 rats per group. The stable COPD rat model was established by the method of smoking and nasal drip (Klebsiella pneumoniae). The samples were taken from the 9th week to the end of the 20th week, and the weight of the rats was measured every week. Routine sections and HE staining were performed on lung tissue and skeletal muscle tissue respectively, and the corresponding pathological changes were observed under light microscope. Lung function of rats was observed by whole body plethysmography (WBP) at week 0, 8 and 20, including tidal volume (VT) and peak expiratory flow, respectively. PEF), 50% tidal volume expiratory flow (EF50). The mRNA expression of IRS-1, Leptin, PGC1-α and PI3K in rat skeletal muscle was detected by qPCR. The expression of PGC-1α, TFAM, IRS-1, PI3K, AKT, p-AKT and Leptin in rat skeletal muscle tissue was detected by WB technique. Results Compared with the Control group, there were a large number of inflammatory cells infiltrated in the alveolar interstitium and bronchus in the Model group, some alveolar walls were broken and fused to form air cavities, and the fibrous network was destroyed. Compared with Model group, the rupture of alveolar wall and destruction of fibroid network were improved in all groups after medication treatment, and the inflammatory cell infiltration in bronchus was reduced, especially in BJF group and Am group. Compared with the Model group, the skeletal muscle pathology of each group after medication treatment could improve the arrangement space, atrophy and fracture of muscle fibers in different degrees, and the cytoplasmic staining of muscle cells was uneven, among which the BJF group had a more significant effect. Compared with Control group, PEF, VT and EF50 in Model group were significantly decreased from week 8 (P<0.01), while PEF and EF50 in BJF, BJF PIO and Am groups were significantly increased (P<0.01). Compared with Control group, mRNA expression levels of IRS-1, PGC1α and PI3K in Model group were significantly decreased(P<0.01), while Leptin mRNA expression level was significantly increased (P<0.01). Compared with Model group, Leptin mRNA expression levels in four medication groups were significantly decreased (P<0.01), while IRS-1 mRNA expression levels in BJF, PIO and BJF PIO groups were significantly increased (P<0.01). The mRNA expression level of PGC-1α in BJF and BJF PIO groups was significantly higher than that in Model group (P<0.01). Compared with Model group, the expression level of PI3K mRNA in BJF, BJF PIO and Am groups was significantly increased (P < 0.01). Compared with Control group, the protein expression levels of PGC-1α, IRS-1 and PI3K in Model group were significantly decreased (P<0.01), while the protein expression level of Leptin was significantly increased (P<0.01). Compared with Model group, the expression level of PGC-1α protein in BJF group was significantly increased (P<0.05), and the expression level of IRS-1 protein in BJF PIO and BJF groups was significantly increased compared with Model group (P<0.05, P<0.01). The expression level of PI3K protein in Am, BJF and BJF PIO groups was significantly higher than that in Model group (P<0.01), especially in BJF PIO group. Compared with Control group, the protein expressions of TFAM and P-Akt in quadriceps femoris tissue of Model group were significantly decreased, while the protein expressions of TFAM and P-Akt were increased in all treatment groups, but there was no statistically significant difference (P>0.05).Conclusion By regulating IRS-1/PI3K signaling axis, Bufei Jiempi can improve the mitochondrial damage of skeletal muscle, increase the expression of mitochondrial coactivator PGC-1α and mitochondrial transcription factor TFAM, enhance mitochondrial biosynthesis, and reduce the pathological damage of lung and skeletal muscle tissue.