We explored the therapeutic effect of photic stimulation (PS) on depression model mice and investigated its possible molecular mechanism. Methods: Mice were subjected to 5 days of forced swimming (FS) to establish a model of depression. They then received PS (frequency 40 Hz, duty cycle 50%, illumination 500 Lux) for 28 days. Depression- and anxiety-like behaviors in mice were assessed using the tail suspension test, forced swim test, and open field test. Western blot was used to detect the expression of synapse-related proteins and related signaling pathway proteins in the prefrontal cortex and hippocampus. Results: Behavioral results indicated that FS successfully induced a depression-like state in mice and that PS improve depressionand anxiety-like behaviors. Western blot showed that, in depression model mice, the levels of postsynaptic density protein 95 (PSD95), NMDA receptor (NR) 1, NR2A, and NR2B in the prefrontal cortex were decreased; the levels of PSD95, NR2A, and NR2B in the hippocampus were decreased. PS was able to restore the expression of the above proteins. The depression model mice prefrontal cortex and hippocampus also displayed a decrease in the expression of brain-derived neurotrophic factor (BDNF) and protein kinase B (Akt) and decreased hosphorylation level; PS was able to reverse the above effects. Conclusion: PS alleviates depression-like behavior and increases synaptic plasticity in depression model mice. Its neuroprotective effect may be achieved at least in part via the BDNF/AKT/GSK3β pathway.