We describe a case of inflammatory myofibroblastic tumor (IMT) that occurred in the retroperitoneum. The patient manifested systemic symptoms, such as intermittent fever, anemia, thrombocytosis, and hypergammaglobulinemia. In order to elucidate the mechanism of intermittent fever in IMT, we analyzed nuclear factor-kappa B (NF-kappaB) activation in peripheral blood mononuclear cells (PBMCs) using flow cytometry, and serum cytokine levels. NF-kappaB activation was observed in the peripheral blood T cells and monocytes/macrophages. Among the measured cytokines, only interleukin (IL)-6 levels were elevated. IL-6 levels during pyrexia in the afternoon were higher than those during apyrexia in the morning. In contrast to IL-6, NF-kappaB activation in PBMCs was lower during pyrexia than during apyrexia; this is considered to be because the activation is subject to negative feedback. The time lag between the increase of IL-6 in the serum and NF-kappaB activation in the PBMCs at the onset of intermittent fever in IMT may provide further insight into the role of cytokines and NF-kappaB activation in febrile inflammatory diseases.