Objective To investigate the effect of lycopene (Lyc) on inflammatory factors and intestinal mucosal barrier function in mice with traumatic brain injury (TBI). Methods Forty-five SPF level of adult male BALB/c mice were randomly divided into sham group, TBI group and TBI+Lyc group, with 15 mice in each group. The TBI model was prepared by modified compression injury model, and the mice in sham group underwent an identical process without mechanical trauma. Each group was further divided into 5 subgroups at 1 d, 2 d, 3 d, 7 d and 14 d after modelling (n=3/subgroup). Mice in sham group and TBI group were treated with 10 mg/kg sunflower oil, and in TBI+Lyc group were treated with 10 mg/kg sunflower oil-dissolved Lyc (concentration 1 mg/ml), daily gavage at a fixed time for 14 d. The inferior vena cava blood and ileum tissue of mice in each subgroup were collected. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) were detected by ELISA, and the serum levels of D-lactic acid (D-LA) and endotoxin were detected by colorimetric method and endpoint chromogenic assay, respectively. Pearson correlation test was used to analyze the correlation between inflammatory factors and intestinal mucosal barrier function indicators. The pathological changes of ileum tissues were observed by HE staining, and the villus height and crypt depth of ileum were measured. Results The serum levels of TNF-α, IL-1β, I-FABP, D-LA, DAO and endotoxin of mice in TBI group and TBI+Lyc group gradually decreased with time, but were obviously higher than those in sham group at different time points (P<0.01 or P<0.001); the serum levels of TNF-α, IL-1β, I-FABP, D-LA, DAO and endotoxin of mice in TBI+Lyc group were significantly lower than those in TBI group at different time points (P<0.01 or P<0.001). Serum TNF-α and IL-1β were significantly positively correlated with I-FABP, D-LA, DAO and endotoxin, respectively (P<0.01). The sham group showed basically normal ileal villi, the structure of ileal villi in TBI group was obviously damaged, and the structure of ileal villi in TBI+Lyc group was basically neat. The ileal villus height and crypt depth of mice in TBI group were lower than those in sham group at each time points (P<0.05), and the ileal villus height and crypt depth of mice in TBI+Lyc group were significantly higher than those in TBI group at different time points (P<0.05). Conclusion Lyc can reduce the levels of inflammatory factors in various stages of TBI mice and may improve the intestinal mucosal barrier function by inhibiting inflammatory response.