This paper reports a case of fulminant pseudo-membranous colitis which did not lead to septic shock. The case was improved by combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin. Direct hemoperfusion using polymyxin B-immobilized fiber has been demonstrated to have excellent therapeutic effects for the treatment of septic shock by removing circulating lipopolysaccharide. In the present case, the combination therapy dramatically improved clinical status of the patient. The clinical improvement occurred in parallel with a decrease in APACHE II score (from 20 to 14 points), serum levels of endogenous cannabinoids (anandamide and 2-arachidonylglycerol), and inflammatory cytokine (interleukin-6). Thus, direct hemoperfusion is strongly recommended in cases of fulminant pseudomembranous colitis, because direct hemoperfusion using polymyxin B-immobilized fiber reduces inflammatory cytokines by absorbing endogenous cannabinoids and, thereby, improves the patient's condition.