Aim of the study: Naoxinqing (NXQ) tablets are derived from persimmon leaves and are widely used in China for promoting blood circulation and removing blood stasis in China. We aimed to explore whether NXQ has the therapeutic effect on ischemic stroke and explored its possible mechanism. Materials and methods: The cerebral artery occlusion/reperfusion (MCAO/R) surgery was used to establish the cerebral ischemic/reperfusion rat model. NXQ (60 mg/kg and 120 mg/kg) were administered orally. The TTC staining, whole brain water content, histopathology staining, immunofluorescent staining, enzyme-linked immunosorbent assay (ELISA) and Western blot analyses were performed to determine the therapeutical effect of NXQ on MCAO/R rats. Results: The study demonstrated that NXQ reduced the cerebral infarction volumes and neurologic deficits in MCAO/R rats. The neuroprotective effects of NXQ were accompanied by inhibited oxidative stress and inflammation. The nerve regeneration effects of NXQ were related to regulating the AMPK alpha/NAMPT/SIRT1/PGC-1 alpha pathway. Conclusion: In summary, our results revealed that NXQ had a significant protective effect on cerebral ischemiareperfusion injury in rats. This study broadens the therapeutic scope of NXQ tablets and provides new neuroprotective mechanisms of NXQ as an anti-stroke therapeutic agent.