Background. Artesunate (AS) is a derivative of artemisinin that can exert anti-inflammatory effects. This study aims to explore the effect of AS on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Methods. The newborn mice were used for experimental ARDS model establishment by intraperitoneal injection of LPS (10 mg/kg) into mice with or without AS (20 mg/kg) pretreatment. After that, the pathological morphology of mouse lung tissue was observed by H&E staining. The content of inflammatory factors in serum was measured by ELISA and mRNA expression and lung tissue was determined by qRT-PCR. The expression of NLRP3 inflammasome and related proteins in lung tissue was confirmed by immunohistochemistry and Western blot. Results. AS treatment effectively alleviated the LPS-induced lung injury and pulmonary edema, and reduced the expression of IL-1β, IL-18, IL-6, IL-8, MCP-1, and TNF-α in serum and lung tissues of experimental ARDS mice. In addition, AS treatment reduced the expression of NLRP3, ASC, and caspase-1 in lung tissues of experimental ARDS mice. Conclusion. AS alleviated LPS-induced lung injury in ARDS mice by inhibiting the activation of NLRP3 inflammasome.