To study the effects of Yiqi Jiedu Fang on mitochondrial energy metabolism related functions in ischemic stroke rats, and to explore the possible protective mechanisms of Yiqi Jiedu Fang on ischemic stroke through intervening the mitochondrial energy metabolism disorder.Methods:Middle Cerebral Artery Occlusion (MCAO) was used. Yiqi Jiedu Fang and its separated formulas were given 15 min prior to MCAO. After 12 h of modeling, mitochondria were extracted. Indexes of mitochondrial three-state respiration rate, four-state respiratory rate, phosphorus-oxygen ratio, respiratory control rate, oxidative phosphorylation rate and other indicators were determined. The protective effect of Yiqi Jiedu Fang on ischemic stroke was evaluated. In addition, the effect of each component of Yiqi Jiedu Fang on anti-ischemic stroke was evaluated by Principal Component Analysis (PCA) and Variable Importance in Projection (VIP).Results:Yiqi Jiedu Fang can improve the mitochondrial respiration related indexes during the pathological process of ischemic stroke. The separated formula of Yiqi Jiedu Fang also has a better effect on ischemic stroke. PCA results showed that compared with other separated formula groups, Yiqi Jiedu Fang group had the best treatment effect. In each separated formula groups, the compatibility of Radix et Rhizoma Ginseng, Fructus Gleditsiae and berberine had the best treatment effect. The results of VIP analysis showed that berberine had the largest contribution to the pathological process of ischemic stroke based on the protection of mitochondrial respiratory function.Conclusion:Yiqi Jiedu Fang can significantly reduce the pathological damage caused by ischemic stroke, whose mechanism may be related to the protection of mitochondrial function.