Previous human studies have investigated the influences of nutritional routes on the serum kinetics of cytokines following intravenous administration of lipopolysaccharide. However, it is unclear whether preoperative nutritional routes influence responses of systemic cytokines in patients after surgery. This study was designed to investigate whether preoperative total parental nutrition (TPN) influences systemic interleukin-6 (IL-6) and interleukin-8 (IL-8) responses in patients following surgery for colorectal cancer. Patients with colorectal cancer received TPN (TPN group, n = 6) or an oral diet (oral group n = 6) for more than 7 d before the operation. Patients in the TPN group received standard TPN. Patients in the oral group received an ordinary hospital diet. Blood samples were collected before the operation, on postoperative day 1 (POD1), POD3, and POD7. Levels of IL-6, IL-8, and C-reactive protein (CRP) in plasma were determined. The characteristics of patients in the TPN and oral groups were comparable. Mean carbohydrate intake was greater (28 versus 19 kCal/kg), and lipid intake was smaller (0 versus 7 kCal/kg) in the TPN group than in the oral group. Plasma CRP levels did not differ between the two groups. Plasma IL-6 and IL-8 levels were marginally higher before the operation and were significantly higher on POD1 in the TPN group than in the oral group. The IL-6 levels showed a positive regression relation with the amounts of blood loss only in the TPN group (P < 0.05, r = 0.881). The slope of the regression line was steeper in the TPN group than in the total enteral nutrition (TEN) group (P < 0.01). In conclusion, routes of nutritional supply have an impact on the production of systemic cytokines after insult. The postoperative systemic IL-6 and IL-8 responses in patients who received standard TPN preoperatively were greater than in patients who received an oral diet. Preoperative nutrition via the enteral route may provide better regulation of cytokine responses after surgery than parenteral nutrition.