Background/Aim: Blood purification therapies have been clinically applied to treat the cytokine-induced pathological responses. The effects of direct hemoperfusion(DHP) with a β<sub>2</sub>-microglobulin (BMG) adsorption column on hypercytokinemia were investigated. Methods: A hypercytokinemia model was prepared by injecting lipopolysaccharide (LPS) into femoral veins of male Wistar rats weighing 250–400 g. The hypercytokinemic rats were connected to the DHP system using a small BMG adsorption column, and time course changes in plasma levels of inflammatory cytokines were then examined. Results: Plasma levels of interleukins (IL) 1β and 6 and tumor necrosis factor alpha (TNF-α) were found to be significantly elevated within 3 h after LPS injection in the control group that underwent extracorporeal circulation without the BMG adsorption column, whereas the increases in plasma levels of IL-6 and TNF-α were significantly inhibited in the group that was treated with the BMG adsorption column. The adsorption rates of cytokines with the BMG adsorption column were 20–40% for IL-1β and IL-6 and 10–85% for TNF-α during treatment for 3 h. Conclusions: These results suggest that the systemic inflammatory response syndrome with hypercytokinemia might be treated with DHP using the BMG adsorption column.