Infections are frequently associated with changes in glucose level, either hyperglycemia or hypoglycemia. The factors that influence glucose change and/or the mechanism(s) that result in altered glucose level during infection are not determined. Therefore, the purpose of this study was to investigate the role of infection-induced changes in IL-6 on blood glucose level. Blood glucose and insulin level were measured in Balb/c mice infected with influenza virus A/PR/8/34 at a dose of 50 ul containing 512 HAU or 1024 HAU (high dose). In addition, anti-IL-6 neutralizing antibody was used to determine the extent to which IL-6 may influence infection-associated changes in glucose or insulin. We found an increase in serum IL-6 at days 1, 2, 3, 5, and 6 post-infection and a significant decline in blood glucose at days 5 and 6 post-infection that was more pronounced with a higher dose of virus. Insulin level increased significantly on day 1 post-infection and then decreased on days 3, 4, and 5 post-infection when a higher dose of virus was used. With the administration of IL-6 neutralizing antibody, there was an attenuation of the decline in glucose level at day 5 post infection, suggesting a potential role for IL-6 in mediating blood glucose during infection. With respect to insulin, the mice treated with IL-6 neutralizing antibody had greater insulin levels than infected mice treated with irrelevant antibody at day 2 post-infection. However at day 5 post-infection, the decline in insulin was not prevented by IL-6 neutralizing antibody suggesting that IL-6 may mediate insulin response at only specific time points during infection. Taken together, the results demonstrate that insulin and glucose levels are altered by infection, and that IL-6 may play a role in mediating these responses. The actual mechanisms by which IL-6 is involved remain to be determined.