Objective To investigate the effect of methane-rich saline on rat acne and its mechanism. Methods Totally 60 SD rats were randomly assigned to 4 groups (n＝15): normal group, acne model group, tretinoin treatment group, or methane-rich saline treatment group. Acne models were established by applying oleic acid once a day and injecting Propionibacterium acnes every other day. No treatment was applied to the normal and acne model groups. The tretinoin treatment group received topical application of tretinoin cream on the affected areas, while the methane-rich saline treatment group was administered with methane-rich saline via oral gavage. Wet/dry weight ratio and histological staining were used to detect the rat ear edema and morphological changes. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to detect apoptosis, enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of inflammatory factors (interleukin［IL］-6, IL-8, tumor necrosis factor α ［TNF-α］, and IL-37), and Western blotting was used to detect the protein expression of superoxide dismutase (SOD), nuclear factor κB (NF-κB), and cysteine aspartic acid specific protease 3 (caspase 3). Results After the treatment with methane-rich saline, the edema and acne were alleviated in rat ears. There were significant improvements in glandular hyperplasia, inflammatory cell infiltration, vascular dilation, hair follicle enlargement, and keratinization for the rats in the methane-rich treatment group. The effect of methane-rich saline was similar to that of tretinoin. The treatment of methane-rich saline could significantly reduce the expression of inflammatory factors such as IL-6, IL-8, and TNF-α, while could significantly increase the expression of anti-inflammatory factor IL-37 and the rate of apoptosis (all P＜0.01). In addition, methane-rich saline treatment could upregulate the expression of SOD, caspase 3, and cleaved caspase 3, while could reduce the expression of NF-κB (all P＜0.01). Conclusion The administration of methane-rich saline has a good therapeutic effect on rat acne, and it may be related to its anti-inflammatory, antioxidant, and pro-apoptotic activities.