Abstract: AIM To investigate whether adiponectin (APN) exerts endothelial protection in response to high glucose/high-fat damage through inhibiting expression of NLRP3 inflammasome. METHODSCultured human umbilical vein endothelial cells (HUVECs) were randomly divided into control group (5 mmol/L glucose, 20 mmol/L mannitol, 48h incubation), high glucose/high-fat group (25 mmol/L glucose, 500μmol/L sodium palmitate, 48 h incubation), control+siRNA group (5 mmol/L glucose, 20 mmol/L mannitol and NLRP3 specific siRNA, 48 h incubation), high glucose/high fat+siRNA group (25 mmol/L glucose, 500 μmol/L sodium palmitate and NLRP3 specific siRNA, 48 h incubation), control+APN group (5 mmol/L glucose, 20 mmol/L mannitol and 2 μg/ml APN, 48 h incubation) and high glucose/high-fat+APN group (25 mmol/L glucose, 500 μmol/L sodium palmitate and 2 μg/ml APN, 48 h incubation). Cells from these groups were harvested for evaluation of cell viability, apoptosis rate and NLRP3 inflammasome expression. RESULTSCompared with control group, cell viability decreased, and NLRP3 inflammasome expression and apoptosis rate increased in high glucose/high-fat group (all P<0.05). These changes were all reversed by NLRP3 specific siRNA and APN (all P<0.05). CONCLUSIONHigh glucose/high fat leads to increased expression of NLRP3 inflammasome, thereby causing cell injury in HUVECs. APN can protect HUVECs by inhibiting expression of the NLRP3 inflammasome.