Abstract： Objective To investigate the effect of arginase1 (ARG1) on cell proliferation and apoptosis of human colorectal cancer (CRC). Methods ARG1gene expression was silenced and over?expressed by transfection of HT29 cells with small interfering RNA (siRNA) and lentiviral vector, respectively. The transfected cells were co?cultured with macrophage M2. The ARG1 gene expression level of the cells in each group was measured by real time RT?PCR. The ARG1 activity of the cells in each group was determined by arginase activity assay. The concentrations of IL?4 and IL?6 in the medium of each group were measured by enzyme?linked immunosorbentassay(ELISA). Cell proliferation and apoptosis of HT29 in each group were assessed by the CCK?8 and TUNEL assay kits,respectively. Results Compared with the control group,the ARG1 activity,IL?4 and IL?6 secretion levels,and proliferation of HT29 cells significantly increased after adding exogenous L?arginine(L?Arg)or high expression of ARG1 gene(P<0.05),whereas the apoptosis of HT29 cells significantly decreased (P<0.05). However, after adding exogenousarginaseinhibitor or applying siRNA to silence the ARG1 gene expression,the ARG1 activity,IL?4 and IL?6 secretion levels,and proliferation of HT29 cells significantlydecreased (P<0.05),whereas the apoptosis of HT29 cells significantly increased(P<0.05). Conclusion ARG1 can induce the secretion of tumor?associated macrophages cytokines IL?4 and IL?6 by promoting arginine degradation in tumor?immune&nbsp;microenvironment,thereby promoting the proliferation and inhibiting the apoptosis of CRC cells. ARG1 may be a new therapeutic target for CRC.