Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with cognitive impairment and neurodegeneration. Objective: To investigate the neuroprotective effects of donepezil on cognitive impairment in a T2DM rat model. Materials and Methods: Twenty four male Wistar rats were divided into three groups: normal control, diabetic control and treatment groups receiving donepezil (4 mg/kg). Cognitive function was assessed using the elevated plus maze novel object recognition test and Morris water maze. Results: Donepezil treatment significantly improved spatial and nonspatial memory, reduced anxiety-like behavior and enhanced cognitive function in T2DM rats. However, donepezil had no effect on blood glucose levels or body weight. Conclusion: This study suggests that donepezil may be a potential therapeutic agent for ameliorating cognitive deficits associated with T2DM, without affecting glucose metabolism or weight management.