To investigate the effect of donepezil on the language function of patients with motor aphasia after acute ischemic stroke. Methods: Thirty patients with motor aphasia and acute ischemic stroke were randomly divided into the donepezil group and the control group with 15 patients per group. Both groups were given conventional anti-platelet therapy and basic treatment, and the donepezil group was additionally given donepezil hydrochloride tablets. Both groups were also given concurrent rehabilitation care and speech therapy. The treatment duration was 2 weeks. All patients underwent routine blood examination, liver and kidney function assessment, and routine coagulation testing. Language fMRI, National Institute of Health Stroke Scale (NIHSS) scoring, and aphasia quotient (AQ) scoring were performed. Results: After treatment, AQ and NIHSS scores of both groups improved compared with those before treatment (all P<0.01), and the improvement in the donepezil group was more significant than that in the control group (all P<0.01). In the donepezil group after treatment, there was enhanced activation in the Broca’s area (BA44/45) of the left middle frontal gyrus (P<0.01, FDR, Ke≥10). The enhanced activation of the Broca's area (BA44/45) produced by donepezil was positively correlated with AQ improvement (P<0.05). Conclusion: Donepezil can promote the activation of the language function area and boost language recovery in acute ischemic stroke patients with motor aphasia; it enhances reestablishment of brain function and is helpful in the recovery from aphasia.