Objective: The inflammatory model in vitro was used to evaluate the anti-inflammatory mechanism of total saponins of Radix Glycyrrhiza. Method: RAW264.7 macrophage line in mice was induced by LPS to set up the inflammatory model. To detect the effect of total saponins of Radix Glycyrrhiza on the release of inflammation factors and the key enzymes for arachidonic acid (AA) metabolism in synthesizing PGE2. Result: The total saponins of Radix Glycyrrhiza could significantly reduce the release of NO, IL-1 and TNF-α in LPS-induced RAW264.7 macrophage line, and obviously decrease the synthesis of PGE2 by inhibiting PLA2 activity and the expression of COX-2. Conclusion: The anti-inflammatory mechanism of total saponins of Radix Glycyrrhiza may be related to reducing the release of inflammation factors in macrophage cell and inhibiting the key enzymes for AA metabolism pathway in synthesizing PGE2.