Objective . Our study aimed to elucidate the correlation of macrophage (mo) with the inflammatory reaction in ulcerative colitis (UC) and the influence of curcumin (Cur) on mo chemotaxis in mice with UC. Methods . A total of 49 patients with UC (research group; RG) admitted between June 2020 and October 2021 and 56 healthy individuals (control group; CG) who visited concurrently were selected as the study participants. The peripheral blood mononuclear cells (PBMCs) were analyzed, and M1-type/M2-type mo and inflammatory factors (IFs) interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha (TNF-a) and transforming growth factor beta (TGF-ss) were detected. In addition, 15 BALB/c mice were purchased and divided into the normal group fed normally, the UC model group established with sodium dextran sulfate (DSS) and the Cur group induced by DSS + Cur feeding. Colon tissue mo was collected from mice to measure mo activity via CCK-8 and to quantify levels of IFs and chemokine CCL2 by polymer chain reaction (PCR)c and Western blotting. Results . The RG had a higher percentage of peripheral blood M1-type mo and a lower percentage of M2-type mo and M1/M2 mo ratio than the CG (P <.05). In the RG, IL-1, IL-6 and TNF-a all increased and were inversely correlated with the ratio of M1/M2 mo, while IL-10 and TGF-ss decreased, with a positive connection with the M1/ M2 mo ratio. In the UC model mice, mo activity increased, but the apoptosis rate decreased. mo activity was lower in the Cur group than in the model and normal groups; mo apoptosis in the Cur group was higher than in the model group but lower than in the normal group. In addition, proIFs increased and anti-IFs decreased in the model group, and Cur also ameliorated this process. Finally, CCL2 and MCP-1 levels in the model group were also increased, while those in the Cur group were lower compared with the model group. Conclusion . In UC, the M1/M2 mo ratio is severely misadjusted, activation of M1-type mo is enhanced and pro-IFs are released in large quantities. Cur can ameliorate the abnormal activation of mo in mice with UC, inhibit mo chemotaxis and alleviate the inflammatory reaction, which may make it a new option for UC treatment in the future. (Altern Ther Health Med. 2023;29(2):97-103)