To investigate therapeutic effects of deep brain magnetic stimulation (DMS) on depressive-like behavior in a post-stroke depression (PSD) rat model and its potential mechanisms. Methods: Total 42 adult male SD rats were screened using sucrose preference test and open field test. They were randomly divided into sham surgery group (Sham group, n=6), stroke group (Stroke group, n=12), PSD group (n=12) , and (PSD + DMS) group (n=12). Cerebral ischemia models were established induced by bilateral common carotid artery occlusion and reperfusion in groups stroke, PSD and (PSD+DMS). The common carotid artery of sham group was only separated without ligation. Groups PSD and (PSD + DMS) accepted chronic mild stress for 3 weeks, while (PSD+DMS) group rats accepted 40 Hz deep brain magnetic stimulation for 40 minutes per day for 2 weeks. The open field test was used to evaluate locomotor activity and anxiety-like behavior, while the sucrose preference test assessed anhedonia-like behavior. Immunofluorescence staining was performed to measure the expression level of Iba-1, a marker of glial cell activation, in the frontal lobe. Protein immunoblotting technique was used to detect the expression of CD11b, a marker of glial cell activation, as well as inflammatory cytokines IL-1 β and TNF-α in the frontal lobe. Results: Treatment with DMS significantly improved depressive-like behavior in the (PSD+DMS) group compared to the PSD group. Glial cell activation and protein expression of inflammatory cytokines IL-1 β and TNF-α were increased in the frontal lobe of the stroke group. In the PSD group, further increase in glial cell activation and protein expression of IL-1 β and TNF-α was observed. However, in the (PSD + DMS) group, glial cell activation was reduced, and protein expression of IL-1 β and TNF-α was decreased. Conclusion: DMS treatment effectively improves depressive-like behavior in PSD rats. Inhibition of glial cell activation and expression of inflammatory cytokines in the frontal cortex may be potential mechanisms underlying its antidepressant effects.