Abstract: Objective: To establish the THP-1 cell lines with leucine carboxyl methyltransferase 1(LCMT1)overexpression by lentiviral vector and study the regulating effect of LCMT1 on THP-1 cells and M2 polarization of THP-1-derived macrophages. Methods: Lentiviral technology was used for the construction of LCMT1 overexpression vectors. Blank group, OE-control group, and OE-LCMT1 group were set up. The green fluorescence of each group of cells was observed by fluorescence microscope. The proliferation levels of each group of cells were detected by the cell counting kit-8(CCK-8) assay. Real-time fluorescence quantitative PCR(RT-qPCR) and western blotting were carried out to evaluate LCMT1 mRNA and protein expression level, and the expression level of PP2Ac methylation-associated protein. THP-1 stable transformation cells were treated by 100 nmol/L phorbol myristate acetate(PMA) for 48 hours and induced to polarize into M0 macrophages, and M0 macrophages were induced to polarize into M2 macrophages by 20ng/mL interferon-4(IL-4) for 48 hours. The mRNA expression of mannose receptor C type 1(MRC-1), CC motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin(CD209) in the polarization markers of M2 macrophages were detected by RT-qPCR. Results: Compared with the blank group, the expression of green fluorescence was expressed in the OE-control group and the OE-LCMT1 group, the proliferation curve was decreased in the OE-control group(P<0.001), and the expression levels of LCMT1and PP2Ac methylation-associated protein differences were not statistically significant in the OE-control group(P>0.05). Compared with the OE-control group, the proliferation curve of the OE-LCMT1 group was decreased(P<0.05), the expression of LCMT1 and PP2Ac methylated proteins was increased(P<0.05), the expression of PPME-1 and PP2Ac demethylated proteins was decreased(P<0.01) and the expression of total PP2Ac protein differences was not statistically significant in the OE-LCMT1 group(P>0.05). Compared with the blank M0group, the mRNA expression levels of MRC-1, CD209, and CCL22 of M2 polarization markers were increased in the blank M2 group(P<0.05). Compared with the OE-control M2 group, the mRNA expression levels of MRC-1, CD209, and CCL22 of M2 polarization markers were reduced in the OE-LCMT1 M2 group(P<0.05). Conclusion: The THP-1 cell lines with LCMT1 overexpression are successfully constructed. LCMT1 overexpression can inhibit the proliferation of THP-1 cells, maintain the total PP2Ac protein levels, enhance the PP2Ac methylation with concomitant reduction in PPME-1 and PP2Ac demethylation, down-regulate the polarization markers of M2 macrophages, and inhibit the polarization of M2 macrophages.