In recent years, depression has emerged as a significant global health concern, prompting many individuals to seek pharmacological interventions. The identification of inflammatory changes in the hippocampus of depressed patients has highlighted a potential therapeutic target. Nevertheless, the effectiveness of medications targeting these specific alterations has yet to be fully substantiated. Preliminary research has suggested the potential benefits of photobiomodulation (PBM) as a treatment for depression, with no significant adverse effects reported. This study utilized near-infrared light at intensities of 50mW/cm² and 300mW/cm² to illuminate mice with chronic mild stress (CMS)-induced depression model, aiming to explore the therapeutic effects of PBM on depression. The findings revealed that when exposed to a power density of 300mW/cm², the mice exhibited enhanced behavioral outcomes, accompanied by decreased levels of inflammatory cytokines such as IL-1α, IL-1β, IL-5, and IL-6 in the hippocampus. A noteworthy association was observed between behavioral manifestations and inflammatory cytokine levels. This study posits that PBM at an intensity of 300mW/cm² is a viable nonpharmacological intervention for depression, as it demonstrates a notable enhancement in depressive symptoms and the regulation of inflammatory mediators within the hippocampal region of the brain. However, this study is constrained by the particular PBM parameters employed; therefore, additional research is necessary to investigate a broader spectrum of doses and treatment durations in order to enhance the therapeutic application and deepen the understanding of the underlying mechanisms.