Graft versus host disease (GVHD) is the major limiting factor after Hematopoietic stem cell transplantation (HSCT). In this study, we report a HSCT-patient who developed arthritis 10-month after allogeneic sibling transplantation, treated with glucosamine-hydrochloride and developed severe acute GVHD within three weeks after the administration of glucosamine. Another HSCT-recipient with an increase in CD33+cells received one dose of donor lymphocyte infusion (DLI). Due to the lack of DLI and based on our experience from the first case, the patient was treated with glucosamine. No sign of relapse was observed in the second patient despite increased number of CD33+ for more than three years. The glucosamine effect was evaluated in seven individuals given the drug for four weeks. The effect of glucosamine treatment was examined by mixed-lymphocyte-reaction (MLR) and the levels of soluble IL-2 receptor (sIL- 2R), TNF-α and IFN-γ were determined. Glucosamine administration exhibited an enhancement in the allogeneic MLR and an increase in the serum levels of sIL-2R, but a decrease in the serum levels of inflammatory cytokines TNF-α and IFN-γ. We conclude that glucosamine may act as an activator of the immune system. In HSCT-patients, glucosamine-mediated immune activation might result in either beneficial or deleterious outcomes. Thus, precautions should be taken when glucosamine is prescribed to HSCT-patients.