Objective:To compare using a rat model of post-stroke depression (PSD) the effect of 28 days of high-intensity interval training (HIIT) with that of medium-intensity continuous training (MICT) on inflammation and neuron apoptosis induced by phosphatase and the deletion of a tensin homolog on chromosome ten (PTEN).Methods:Male Wistar rats were randomly divided into a SHAM, a PSD, an MICT and an HIIT group. Except in the SHAM group, blood flow in the middle cerebral artery was blocked for 90 minutes followed by reperfusion. Repeated but unpredictable mild stimulation was then applied to induce depression. The rats in the HIIT and MICT groups started 28 days of training 24 hours after the successful modeling. The running platform speed was adjusted according to the lactic acid threshold and the maximum speed was measured weekly. In the SHAM group the common carotid artery, internal carotid artery and external carotid artery were only separated without occlusion and there was no depressive stimulation. Any improvements in depression were detected using the sucrose preference test and the forced swimming test. The expression of PTEN, nuclear factor kappa B (NF-κB) and nod-like receptor protein 3 (NLRP3) were detected using western blotting. The expression of cysteine-containing, aspartate-specific proteases (caspase-3) was detected immunohistochemically.Results:Compared with the SHAM group, the PSD group′s average immobility time in the swimming test was significantly longer and its average sucrose consumption was significantly less. Compared with the PSD group, the rats in the MICT and HIIT groups showed, on average, significantly more sucrose consumption and shorter immobility time, indicating that their depression was ameliorated. The expression of PTEN, NF-κB and NLRP3 in the MICT and HIIT groups was, on average decreased significantly compared with the PSD group. The HIIT group′s averages were at the same time significantly lower than those of the MICT group. Average caspase-3 levels in the dentate gyrus of the MICT and HIIT group rats were significantly lower than in the PSD group, with the HIIT group′s average significantly lower than that of the MICT group.Conclusions:Both high- and medium-intensity interval training show neuroprotective effects. They inhibit activation of the PTEN/NF-κB/NLRP3 pathway, reducing the expression of apoptotic proteins in the hippocampus. Higher intensity training has a more obvious antidepressant effect.