〔Abstract〕 Objective To investigate the effect of Rehmannia on neuronal apoptosis after ischemic stroke through Janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) pathway and its related mechanism. Methods A total of 40 healthy SD rats were selected and randomly divided into sham operation group, model group, Rehmannia group and positive control group. The rat model of ischemic stroke with middle cerebral artery occlusion was established by modified thread thrombus method. After the model was established, relevant drug administration was carried out. Morris water maze test was used to evaluate the learning and memory ability of rats. Zea-longa score and triphenyltetrazolium chloride (TTC) staining were used to evaluate the brain injury of rats. The hippocampal tissues of rats were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expressions of apoptosis-related protein BAX, apoptosis-related protein Bcl-2, JAK2/STAT3 pathway proteins P-JAK2 and P-STAT3 were detected by Western blot. Results Compared with the model group rats, the Rehmannia group rats could increase the number of transplatform and shorten the escape latency, and the score of nerve function deficit was significantly decreased (P < 0.05), the infarct area of brain tissue was significantly decreased (P < 0.05), and the level of neuron apoptosis in hippocampus was significantly decreased (P < 0.05). The expression level of BCL-2 was increased and the protein expression levels of BAX, p-JAK2 and p-STAT3 in hippocampus nerve cells were significantly decreased (P < 0.05). Conclusion The traditional Chinese medicine Rehmannia can improve the cognitive impairment and reduce the neuronal apoptosis in ischemic stroke rats, and its mechanism may be related to the regulation of apoptosis related signaling pathway JAK2/STAT3.