Background and Objective: Increasing evidence has shown that diabetes induces cognitive dysfunction and impairs learning and memory. Berberine is an isoquinoline alkaloid and vitamin E is a fat-soluble antioxidant with multiple pharmacological effects on diabetes. Thus, we investigated the effect of Berberine hydrochloride and vitamin E on diabetes-induced cognitive dysfunction in rats. Materials and Methods: 48 male Wistar rats were randomly selected and allocated in 6 control groups: control treated with vitamin E (30mg/kg), diabetic and Berberine-treated diabetic group (100mg/kg), vitamin E-treated diabetic group (30mg/kg) and a diabetic group treated with both vitamin E and Berbrine. Diabetes was induced by STZ administration at dose of 55mg/kg through Intraperitoneal injection route. Berberine hydrochloride and vitamin E were administered per os, respectively at doses of 100 and 30 mg/kg/day 1 week after STZ injection for a period of 6 weeks. 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