Aim To study the protective effect and oxiracetam on rats with cerebral infarction and the role of HIF-1α/AMPK/HSP70 signaling pathway. Methods Adult male SD rats were randomly divided into sham group, cerebral infarction group, oxiracetam group, oxiracetam+YC-1 group, oxiracetam+8-bAMP group and oxiracetam+Que group. The model of cerebral infarction was established by thread embolization. Oxiracetam group was given tail vein injection of 200 mg/kg oxiracetam, Oxiracetam+YC-1 group, Oxiracetam+8-bAMP group, Oxiracetam+Que group were given tail vein injection of HIF-1α inhibitor YC-1, AMPK inhibitor 8-bAMP, HSP70 inhibitor Quercetin separately on the basis of Oxiracetam tail vein injection. After 14 days of intervention, cerebral infarction volume, behavioral parameters, oxidative stress index and HIF-1α/AMPK/HSP70 pathway molecule in brain were measured. Results Compared with cerebral infarction group, the volume of cerebral infarction significantly reduced, the standing time of balance beam and walking time of balance beam significantly prolonged, the contents of ROS, MDA, 8-OHdG in brain tissue significantly decreased, the contents of SOD and GPx and the expressions of Nrf2, HO-1, AMPK and HSP70 in brain tissue significantly increased. Compared with the oxiracetam + YC-1 group, oxiracetam + 8-bAMP group and oxiracetam + Que group, the contents of ROS, MDA, 8-OHdG in brain tissue significantly increased, the contents of SOD, GPx and the expression of Nrf2, HO-1 significantly decreased(P＜0.05). Conclusion Oxiracetam can alleviate cerebral infarction injury in rats by activating HIF-1α/AMPK/HSP70 pathway.