Abstract: Objective To explore the effects of Ghrelin on the hippocampus neuronal apoptosis and the cognitive function of diabetic rats. Methods 40 SD male rats were meanly divided into normal group, diabetic modle group, Ghrelin treatment group, Ghrelin and D-lys-3-GHRP-6 treatment gooup randomly. Streptozotocin-diabetic rats model were established, diabetic rats with depression were screened by open-field test, learning and memory behaviors were measured using a spatial version of the Morris water maze test. The mRNA level of caspase-3 was examined by RT-PCR. The protein expression of capase-3, BCL-xl were examined with immunohistochemical method. Meanwhile the hippocampus neuronal apoptosis were measured by TUNEL. Result Comparing to the normal group, learning and memory level of diabetic group and Ghrelin + D-lys-3-GHRP-6 trreatment group decreased transparently（P<0.05）, the mRNA and protein level of caspase-3 in hippocampal neuron increased and the protein expression of BCL-xl were descendent (P<0.05), the number of neuronal apoptosis increased markedly（P<0.05）. Learning and memory level in the Ghrelin treatment group were much better than diabetic modle group（P<0.05）, the changes of caspase-3 in hippocampus significantly reduced（P<0.05）and the expression of BCL-xl in hippocampus inceased in the Ghrelin treatment group and the number of apoptotic neurons of the hippocampus was decreased remarkably (P<0.05).. Conclusion Ghrelin could improve cognitive ability in diabetic rats ,which increased the expression of BCL-xl and decreased the expression of caspase-3 to inhibit hippocampus neuronal apoptosis.