Children with type 1 diabetes mellitus (DM) are at risk of developing cognitive difficulties. Although a diabetes onset of patient influences cognitive difficulties, synaptic properties related to the age of diabetes onset remain unknown. Here we showed that synaptic plasticity including long-term potentiation (LTP) or long-term depression (LTD), and excitatory synaptic transmission at Schaffer collateral-CA1 (SC-CA1) synapses in hippocampal slices were affected by age of onset in rats with streptozotocin-induced diabetes (STZ-rats), compared with age-matched control rats. LTP was impaired and the ratio of AMPA receptor-mediated EPSCs relative to N-methyl-d-aspartate (NMDA) receptor-mediated EPSCs (the AMPA/NMDA ratio) decreased in young adult-onset STZ-rats, whereas LTD was impaired and both AMPA receptor-mediated and NMDA receptor-mediated EPSCs increased in juvenile-onset STZ-rats. Furthermore, impaired LTD of juvenile-onset STZ-rats was restored with an NMDA receptor antagonist. These results suggest that the pathophysiology of diabetes-induced cognitive difficulties varies with the age of diabetes onset. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.