Aims: It is emerging a correlation between diabetes and brain pathologies, such as Alzheimer's Disease (AD), associated with decreased synaptic plasticity and cholinergic dysfunctions. We investigated whether diabetes and electroacupuncture (EA), affecting cholinergic neurotransmission at septo-hippocampal terminals, could alterate dentate gyrus (DG) long-term potentiation (LTP). Methods: After induction of type 1 diabetes in rats by streptozotocin (STZ), EA was performed for 3 weeks starting 1 week after STZ treatment. We performed electrophysiological studies in DG by stimulating medial-perforant pathway. LTP was evoked by high-frequency stimulation (HFS) consisting of eight trains, each of eight stimuli at 200 Hz, and an inter-train interval of 2 s. The occurrence of LTP was studied in HP slices from controls, STZ and STZ+EA rats. The role of muscarinic modulation of LTP was investigated by carbachol (CCh) stimulation of HP slices. The specific role of M1 acetylcholine receptor (M1AChR) was studied by the M1-antagonist telenzepine (TZ) both in bath superfusion and in vivo. Results: Our results demonstrated an impairment of LTP in STZ rats compared to controls. EA restored LTP in STZ rats. CCh counteracted EA effects in HP from diabetic animals. TZ treatment of diabetic HP slices or diabetic animals in vivo also abolish EA effects on LTP. Conclusions: Our results suggest a possible role for EA in modulating LTP at DG, by acting on the regulation of cholinergic neurotransmission. Our data point to a M1AChR-mediated EA action. Therefore, EA could represent an useful tool for progressive cognitive decline associated with diabetes.