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Objective: To explore the therapeutic potential of Cordyceps sinensis (Berk.) Sacc. (C. sinensis, Dong Chong Xia Cao) in an ischemic stroke (IS) model and predict its possible mechanism through network pharmacology. Methods: Thirty-three Sprague–Dawley rats were randomly divided into the Sham, model, and C. sinensis groups. After 5 days of pre-treatment, the model group and the C. sinensis group were subjected to middle cerebral artery occlusion (MCAO) modeling. Effect of C. sinensis on MCAO rats was evaluated by comparing cerebral infarct size, neurological function, cerebral water content, pathological changes, and certain biochemical indicators. Intersection targets between C. sinensis and IS was screened using network pharmacology analysis. Relationship among core components, targets and pathways of C. sinensis in treating IS was constructed through network pharmacology analysis and further verified by molecular docking. Finally, the DAVID v8.8 database was used for performing GO analysis and KEGG pathway enrichment analysis by importing the intersection targets. Results: Compared with the model group, C. sinensis significantly reduced the volume of cerebral infarction (P = .026), the cerebral water content (P = .0013), the mNSS score (P < .001), and the levels of IL-17 (P = .031), TNF-α (P = .016), MDA (P = .014), and glutamate (P = .014) in serum, while upregulating the level of SOD in serum and improving the pathological morphology in MCAO rat ischemic brains. The results of network pharmacology analysis showed that core targets (such as CASP3, PTGS2, and PPARG) and the main enrichment pathways (IL-17, AGE-RAGE, and TNF signaling pathways) were regulated by 30 chemical components of C. sinensis, which effectively treated IS in MCAO rats. Conclusion: The results of this study showed that C. sinensis effectively interfered with MCAO rats, and the mechanism may be related to the regulation of blood lipids and to anti-apoptosis and anti-inflammatory effects.