Abstract: Objective To investigate the protective effects of Apelin-13 on the thrombin-induced HT-22 cells injury model and examine whether the effects depend on the PTEN/Akt/FoxO3a pathway. Methods: The cells were treated with thrombin and/or Apline-13, and were randomly divided into control group, Thrombin treated group (Thrombin) and Thrombin combined with Apelin - 13treated group (Thrombin + Apelin - 13), relevant tests were performed after 9 h treatment. Immunofluorescence and western blotting were utilized for measuring the autophagosomes and the expression level of autophagy related proteins (PTEN, Akt, p-Akt, FoxO3a). Results: Compared with the thrombin group, the HT-22 cells had larger cell volume and more neurite outgrowth after Apelin-13 treatment, the protein levels of LC3-Ⅱ/LC3-Ⅰ, p-Akt and immunofluorescence intensity of autophagosomes were also decreased by Apelin-13 administration. However, the expression of PTEN and FoxO3a were increased after Apelin-13 treatment . Conclusion: All these results revealed that Apelin-13 could suppress autophagy after thrombin-induced injury in HT-22 cells through PTEN/Akt/FoxO3a pathway. The autophagy involved in the mechanism of Apelin-13 rescue the subsequent damaged after thrombin-induced injury in HT-22 cells