Background <p>Pyroptosis has been reported to occur in several diseases, such as atherosclerosis, nonalcoholic steatohepatitis, and endometriosis. Although fucoxanthin has several biological properties (particularly anti-inflammatory properties), the mechanism through which fucoxanthin modulates or inhibits pyroptosis pathways is unclear. The present study aimed to determine whether fucoxanthin ameliorate endometriosis by preventing macrophage pyroptosis.</p> Methods and results <p>A model of localized cell death in M2 macrophages induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) was developed. Fucoxanthin decreased the ATP- and LPS-induced pyroptosis of M2 macrophage. Pretreatment with fucoxanthin alleviated oxidative stress and decreased the release of Reactive Oxygen Species (ROS) and LDH from M2 macrophages. Fucoxanthin pretreatment decreased the mRNA expression levels of GSDMD, NLRP3, caspase-1, IL-18, and IL-1β and inhibited the activation of the NLRP3 inflammasome and decreased the protein expression levels of Caspase-1 and GSDMD. In addition, fucoxanthin treatment reduced inflammatory signalling and decreased the expression and release of the IL-18 and IL-1β inflammatory factors.</p> Conclusions <p>Fucoxanthin prevents macrophage pyroptosis by inhibiting the mammalian target of rapamycin (mTOR), protein kinase B (AKT), and phosphatidylinositol 3-kinase (PI3K) signalling pathway.</p> Clinical Trial Registration <p>Clinical trial number: not applicable</p>