〔Abstract〕 Objective To investigate the immunomodulatory effects of umbilical cord mesenchymal stem cells(UC-MSCs) modified by miR-125b-5p through JAK2/STAT3 pathway on systemic lupus erythematosus(SLE). Methods UC-MSCs were isolated and cultured under aseptic conditions; Peripheral blood mononuclear cells(PBMCs) were separated from SLE patients by density gradient centrifugation. The relative expressions of IL-17A, Foxp3, IFN-γ, IL-4 genes in PBMCs cultured with UC-MSCs for 48 h were detected by RT-qPCR; The relative expressions of JAK2, p-JAK2, STAT3, p-STAT3 and IL-18 proteins in kidney tissues of MRL/lpr mice were detected by western blot. Results Compared with the PBMCs culture group, the expression of IFN-γ and IL-17A and the proportion of Th17/Treg cells were significantly down-regulated in UC-MSCs+miR-125b-5p group, UC-MSCs+miR-NC group and UC-MSCs group(P<0.01), the expression of the proportion of Th1/Th2 cells(P<0.05) was down-regulated in UC-MSCs+miR-125b-5p group and UC-MSCs+miR-NC group; Compared with the untreated group of MRL/lpr mice, the relative expressions of JAK2, p-JAK2, STAT3, p-STAT3 and IL-18 proteins in kidney tissues of MRL/lpr mice were significantly down-regulated in UC-MSCs+miR-125b-5p group(P<0.01), and the relative expressions of IL-18 proteins was significantly down-regulated in UC-MSCs+miR-NC group and UC-MSCs group(P<0.01). Conclusion miR-125b-5p plays a synergistic role in UC-MSCs, which regulates the differentiation of Th2 cells in PBMCs of SLE patients and the relative expressions of p-JAK2/JAK2, p-STAT3/STAT3, and IL-18 proteins in kidney tissues of MRL/lpr mice. UC-MSCs modified by miR-125b-5p may play immunomodulatory effect on SLE by JAK2/STAT3 signaling pathway.