Objective To investigate the inhibitory effect of gallic acid (GA) on lipopolysaccharide (LPS)-induced inflammatory responses in human THP1 macrophages. Methods THP1 monocytes were differentiated into macrophages with phorbol myristate acetate (PMA) and then the macrophage inflammation model was established with LPS induction，and GA was given in different concentrations. The safe concentrations of LPS and GA on THP1 cells were screened by CCK-8 method，and the normal group, model group (100 μg/L LPS ) and GA group（100 μg/L LPS + different concentrations of GA）were set up. ELISA was used to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in the cell culture fluid of each group. Microplate method was used to detect LDH activity and NO content in cell cultures of each group, and fluorescence staining was used to detect ROS levels, cell damage and changes in mitochondrial transmembrane potential in each group.Western blotting assay was performed to detect the levels of cyclooxygenase-2 (COX-2), HMGB1,c-Jun amino-terminal kinase (JNK), extracellular-regulated protein kinase (ERK), P38 mitogen-activated protein kinase (P38), nuclear transcription factor-κB (NF-κB), NOD-like receptor protein 3(NLRP3), Caspase-1,IL-1β、Gasdermin D(GSDMD). Results Compared with the normal group, the secretion of IL-6, TNF-α, IL-1β and NO in cell cultures was increased in the model group (P<0.05), and the secretion of COX-2, HMGB1, p-ERK, p-JNK, and p-P38 and p-NF-κB, NLRP3, Caspase-1, IL-1? protein expression was elevated (P<0.05), the expression level of GSDMD protein activation fragment was reduced (P<0.05), ROS generation and cellular damage were significantly increased, mitochondrial transmembrane potential was significantly lower than that of the normal group, and the activity of LDH was elevated (P<0.05); in comparison with the model group, the cell culture fluid of the GA group IL-6, TNF-α, IL-1β and NO secretion were decreased (P<0.05), COX-2, HMGB1, p-ERK, p-JNK and p-P38 and p-NF-κB, NLRP3, Caspase-1, IL-1β protein expression was decreased (P<0.05), GSDMD protein activation fragment expression level was increased (P<0.05), ROS generation and cellular damage were decreased, mitochondrial transmembrane potential was gradually increased, and LDH activity was decreased (P<0.05).Conclusion GAhas an inhibitory effect on LPS-induced inflammatory response in THP1 macrophages, and its anti-inflammatory mechanism may involve MAPK and NF-κB signalingpathways.