OBJECTIVE: To study the anti-inflammatory effect of ampelopsin F (AMPF) on lipopolysaccharide (LPS)-induced inflammatory model cells and its mechanism. METHODS: Using RAW264.7 cell as model cell, CCK-8 assay was used to determine the activity of cell after treated for different duration (24, 48, 72 h) with different concentration (100, 40, 20, 10, 5 μg/mL) of AMPF. Then the cells were divided into control group, model group and AMPF high-dose, medium-dose and low-dose groups (40, 20, 10 μg/mL). They were cultured without or with relevant AMPF solution for 24 h [Except for normal control group, other groups received LPS (1 μg/mL) to induce inflammatory model after cultured for 1 h]. The contents of IL-1β, IL-6, TNF-α and NO, the protein expression of COX-2 and iNOS were detected in cell culture supernatant. RESULTS: After cultured for 24 h, survival rates of cells in AMPF groups (100, 40, 20, 10, 5 μg/mL) were all higher than 90%, showing no obvious cytotoxicity of AMPF. Compared with model group, the content of IL-1β and the protein expression of iNOS were decreased significantly in AMPF high-dose, medium-dose and low-dose groups; the contents of IL-6, TNF-α and NO were decreased significantly in AMPF high-dose group; the protein expression of COX-2 were decreased significantly in AMPF high-dose and medium-dose groups, with statistical significance (P<0.05 or P<0.01), in dose-dependent manner. CONCLUSIONS: AMPF shows significant anti-inflammatory effect on LPS-induced RAW264.7 cell inflammation, the mechanism of which may be associated with regulating the expression of COX-2 and iNOS, inhibiting the release of NO and decreasing the contents of IL-1β, IL-6, TNF-α and NO.