The pathology of multiple myeloma (MM) includes the involvement of chemokines, cytokines and growth factors secreted by MM and other cells. Vascular endothelial cells and/or the hemostatic-coagulatory system are thought to play an important role in the development of MM. Ninjin-youei-to (NYT) is a traditional Chinese medicine made from the extracts of 12 plants that affects immunity and inflammation. The effects of NYT on plasma concentrations of various biomarkers were therefore investigated in MM patients. The plasma concentrations of RANTES, sVCAM-1, sE-selectin, Ang-2, VEGF, PAI-1 and PDMP were higher in MM patients than in healthy controls. Melphalan-prednisone (MP) treatment of MM patients for 6 months significantly decreased plasma concentrations of RANTES, sE-selectin, PAI-1 and PDMP, but did not significantly alter plasma concentrations of IL-6, TNF, MCP-1, sVCAM-1, Ang-2 and VEGF. Although treatment with NYT alone did not significantly alter the concentrations of any biomarker, it enhanced the MP-associated reduction of many biomarkers, as well as significantly reduced the concentrations of some markers, such as sVCAM-1, Ang-2 and VEGF, not reduced by MP alone. Furthermore, MP plus NYT significantly improved immunoglobulin concentrations compared with administration of MP alone, and regimens that included NYT significantly improved general fatigue. These results suggest that NYT possess an immunotherapeutic effect or can enhance the effects of MP in patients with MM.