To analyze water extract of Sonchus Oleraceus on the regulation of related pathways of body's inflammatory, and further investigate the mechanism of it. Methods:A total of 100 healthy male SD mice were randomly divided into 10 groups (n＝10). Five groups of mice were treated with ear swelling experiment, and foot swelling experiment was used in mice of another five groups. In ear swelling test and foot swelling experiments, model group and dexamethasone group (2 mg/kg) positive drug group, water extract of Sonchus 0.26 g/10 g dose group, water extract of Sonchus 0.13 g/10 g dose group and water extract of Sonchus 0.065 g/10 g group. The levels of COX-2, p38 MAPK, TNF-α and IL-6 in different serum and inflammatory tissue fluid of different groups were detected. Results:There were significant differences of ear swelling degree in different dose groups. The inhibition mice were 73.12%, 43.62%, 28.83%, respectively. Compared with the model group, mice auricle swelling with water extract of Sonchus oleraceus of different dose was inhibited, and with the increase of the dose, inhibition effect was enhanced. There were significant differences in the swelling degree of paw in different dose groups, and the inhibition rates were 54.80%, 35.09%, 29.73% respectively in each group. Compared with the model group, mice paw swelling with Sonchus oleraceus water extract of different dosage were inhibited, and with the increase of the dose, inhibition effect was enhanced. Effects of water extracted of Sonchus oleraceus related factors on the inflammatory tissue of mice in the solution: positive control group, Sonchus oleraceus water extracted dose and high dose group with COX-2, p38 MAPK, TNF-α, IL-6 levels compared with the model group, and there was significant difference (P<0.05). Effects of water extract of Sonchus oleraceus of inflammation related factors in sera of mice: positive control group, Sonchus oleraceus water extract in dose of COX-2 and p38 MAPK levels compared with the model group, and there was significant difference (P<0.05); The positive control group, water extract of Sonchus oleraceus middle dose group and high dose group of TNF-α and IL-6 levels compared with the model group, there was significant difference (P<0.05). Conclusion:Anti-inflammatory mechanism of water extract of Sonchus oleraceus involves many aspects and inflammatory factors in the process of inflammation, which is expected to be developed into new anti-inflammatory drugs effectively, providing new medicinal and therapeutic resources for the prevention and treatment of inflammatory diseases.