Abstract Telmisartan, an angiotensin II type 1–receptor blocker (ARB), has been reported to exert beneficial effects on the central nervous system (CNS) in streptozotocin (STZ) - induced diabetic mice. However, the effect of telmisartan on cognitive impairment associated with type 2 diabetes is not well known. Here, we investigated the effects of telmisartan on memory impairment in a mouse model with defects in insulin sensitivity and secretion, namely highfat diet (HFD) /STZ-induced diabetic mice. Our data showed that STZ / HFD diabetic mice, characterized by hyperglycemia and hypoinsulinemia, performed poorly on Morris water maze (MWM) test. Such learning and memory impairment was accompanied by increased β -amyloid peptide 42 (Aβ42), amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme (BACE1), the receptor for advanced glycation end products (RAGE) and nuclear factor -κB (NF-κB) signaling in brain. Treatment with telmisartan significantly improved learning and memory in the diabetic mice and decreased Aβ42, APP, BACE1 RAGE and NF-κB signaling in the brain without affecting hyperglycemia and hypoinsulinemia. It is concluded that telmisartan may be considered as a potential pharmacological agent for the management of cognitive dysfunction in type 2 diabetes.