Objective: To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia. Methods: The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion, MCAO) was established by suture occlusion. Except the sham operation group, the other groups were randomly divided into model group and Xingnaojing group. The rats in Xingnaojing group were intraperitoneally injected with Xingnaojing injectionaccording to 0.18ml/100g, and the sham operation group and model group were given the same amount of normal saline respectively. 24 hours after the establishment of the model, the morphological changes of neurons in the penumbra of the rats were observed by Nissl staining, the ultrastructural changes of neurovascular unit (Neurovascular unit, NVU) were observed by transmission electron microscope (Transmission electron microscope, TEM)), and the apoptosis of the ischemic penumbra was detected by in situ apoptosis (TdT-mediated Dutp Nick-End Labeling, TUNEL)). Magnetic resonance imaging was used to observe the ischemic evolution of the penumbra of the same rat at 4.5 h and 24 h, respectively. Results: Compared with the sham operation group, the number of neurons in the model group was significantly reduced, the structure of Nissl corpuscles was destroyed, the outline was blurred or disappeared, the pathological morphology of NVU ultrastructure was obviously damaged under transmission electron microscope, a large number of apoptotic cells could be seen in the model group by TUNEL staining(P<0.01), and magnetic resonance imaging showed that there was a large area infarction in the brain tissue of the model group. Compared with the model group, the pathomorphology of neurons and NVU ultrastructure in Xingnaojing group was significantly improved, the number of apoptotic cells was significantly decreased(P<0.01), and the loss rate of penumbra was significantly lower in Xingnaojing group(P<0.05). Conclusion: Xingnaojing injection can improve the state of neurons in ischemic penumbra, reduce the injury of glial cells and microvessels, inhibit apoptosis, promote the transformation of penumbra in rats with acute cerebral ischemia, and save part of penumbra to some extent. it has a certain protective effect on the brain tissue of penumbra in the acute stage of cerebral ischemia.