Objective: This study aims to investigate the effects and potential mechanisms of liraglutide (Li) on macrophage polarization induced by silica (SiO2). Methods: THP-1 cells were induced to adhere to macrophages, and five groups were established: Control group, SiO2 group, SiO2+Li group (with Li concentrations of 10 nM, 100 nM, 1000 nM). The cytotoxicity of Li on the macrophages was assessed by using a cell counting kit (CCK)-8 assay. ELISA was employed to analyze the levels of interleukin (IL) -1β, IL-10 and transforming growth factor-β1 (TGF-β1) in the macrophage culture. Western blot assay was used to determine the expression levels of NLRP3, Caspase-1 p20, Arg-1. Mitochondrial membrane potential in the macrophages was detected by using JC-1 fluorescent probe staining. Reactive oxygen species (ROS) levels in the macrophages from all groups were measured by using DCFH-DA probe. Results: Compared to Control group, the expression levels of NLRP3, Caspase-1 p20 and Arg-1 were significantly elevated in SiO2 group. In comparison to SiO2 group, there was a significant decrease in the expression levels of NLRP3, Caspase-1 p20 and Arg-1 in SiO2+Li (10 nM) group, SiO2+Li (100 nM) group and SiO2+Li (1000 nM) group. The level of IL-1β in SiO2 group was significantly higher than that in Control group [(127.00±17.05) pg/mL vs. (37.72±10.23) pg/mL]. In the SiO2+Li groups with different concentrations (10 nM, 100 nM, 1000 nM), IL-1β levels were (77.40±12.55) pg/mL, (64.74±6.86) pg/mL and (41.55±12.74) pg/mL respectively, showing statistically significant differences compared with SiO2 group . The level of IL-10 in SiO2 group was significantly higher than that in Control group [(212.70±6.97) pg/mL vs. (70.88±3.21) pg/mL]. In the SiO2+Li groups with different concentrations (10 nM, 100 nM, 1000 nM), IL-10 levels were (127.80±7.70) pg/mL, (110.80±6.53) pg/mL and (85.13±7.17) pg/mL respectively, showing statistically significant differences compared with SiO2 group. The level of TGF-β1 in SiO2 group was significantly higher than that in Control group [(854.60±98.00) pg/mL vs. (268.40±19.29) pg/mL]. In the SiO2+Li groups with different concentrations (10 nM, 100 nM, 1000 nM), TGF-β1 levels were (511.20±66.53) pg/mL, (386.70±32.30) pg/mL and (308.00±89.20) pg/mL respectively, showing statistically significant differences compared with SiO2 group. The intracellular mitochondrial membrane potential decreased in SiO2 group when compared to Control group. However, it increased in SiO2+Li (10nM) group, SiO2+Li (100 nM) group and SiO2+Li (1000 nM) group when compared to SiO2 group. The relative fluorescence intensity of ROS was higher in SiO2 group than that in Control group with statistical significance observed. Additionally, the relative fluorescence intensity of ROS was lower in SiO2+Li (10 nM) group, SiO2+Li (100 nM) group and SiO2+Li (1000 nM) group than that observed for SiO2 group. Conclusions: Liraglutide exhibits the potential to ameliorate mitochondrial dysfunction, alleviate ROS oxidative stress, inhibit NLRP3 inflammasome activation, and suppress M2-type macrophage polarization induced by SiO2.