Objective To investigate effects of Ghrelin on learning and memory processes, hippocampal neuron synapses and growth hormone secretagogue receptor (GHS-R) expression in mice. Methods Twenty male mice (8 weeks old) were randomly divided into the Ghrelin-treated and control groups (10 mice/group) in which Ghrelin or equal quantity saline was intraperitoneally injected, respectively. The ability of spatial learning and memory were tested with Morris water maze (MWM), expression of Ghrelin receptor GHS-R in hippocampus with immunohistochemical method and image analysis, and structural changes of synapsis in the hippocampal region by transmission electron microscope.Results In the MWM experiment, compared with the control group, the escape latency of the treated group on the day 2, 3 and 4, was significantly shortened, the times crossing hidden platform markedly increased (EM>P/EM> <0.05),expression of GHS-R immunoreactive products increased obviously in hippocampus (EM>P/EM> <0.05),and numbers of hippocampal neuron synapses in the CA3 region were also strikingly increased in the Ghrelin-injected group compared with the control group (EM>P/EM> <0.05).Conclusion Ghrelin may increase the synapse numbers of the hippocampal region, by binding the GHS-R in hippocampus, and subsequently enhance spatial learning and memory