To determine whether insulin administration modulates the systemic inflammatory response in infants undergoing cardiac surgery with cardiopulmonary bypass, 60 infants undergoing cardiopulmonary bypass were randomly assigned into a routine therapy group or to an intensive insulin therapy group with 30 infants in each group. Plasma IL-1beta, IL-6, IL-10, and TNF-alpha levels were determined before anesthesia, at the initiation of cardiopulmonary bypass, and at 0, 6, 12, 24, and 48 h after cardiopulmonary bypass. Nuclear factor-kappaBp65 expression and IkappaB expression in peripheral blood mononuclear cells were also measured by Western blot analysis. TNF-alpha, IL-1beta, IL-6, and IL-10 levels were all elevated after the initiation of cardiopulmonary bypass. However, TNF-alpha, IL-1beta, and IL-6 levels were significantly attenuated in the intensive insulin therapy group compared to those in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Meanwhile, plasma IL-10 levels were significantly higher in the intensive insulin therapy group than in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Accordingly, Nuclear factor-kappaBp65 expression and IkappaB expression were significantly increased after initiation of cardiopulmonary bypass in both groups (p<0.05 or <0.01). The expression of Nuclear factor-kappaBp65, which induces the transcription of pro-inflammatory cytokines was significantly attenuated in the intensive insulin therapy group (p<0.05 or <0.01). Meanwhile, the expression of IkappaB, an inhibitor of NF-kappaB, was significantly higher in the intensive insulin therapy group (p<0.05 or <0.01). These results suggested that intensive insulin therapy may attenuate the systemic inflammatory response in infants undergoing cardiopulmonary bypass.