The effect of prolonged overtraining on cytokine kinetics was compared with moderate exercise in the present study. Male Wistar rats were randomly divided into control sedentary (C), moderate trained (MT), (V=20 m/min, 30 min/day for 6 days a week, 8 weeks), overtrained (OT) (V=25 m/min, 60min/day for 6 days a week, 11 weeks) and recovered overtrained (OR) (OT plus 2 weeks recovery) groups, (n=6 for each group). Immediately, 24 hr and 2 weeks (in OR) after last bout of exercise blood samples were obtained. The plasma concentrations of TNFα, IL-6, IL-10, IL-4 and IFN were measured by ELISA method. Immediately after last bout of exercise the following findings were observed; IL-6, IL-10 and TNFα concentrations increased in OT and OR groups compared with control (P<0.05-P<0.001). Serum level of IL-4 decreased (P<0.01) but IFN increased (P<0.05) in MT group vs. control. In addition, circulatory levels of TNFα, IL-6, IL-10 and IL-4 were higher but the IFN concentrations were lower in OT and OR groups than MT group (P<0.05-P<0.01). The IFN-γ/IL4 ratio was significantly increased in MT (P<0.01) while it decreased in OT group. There were not statistical differences in TNFα, IL-6, and IFN levels between different time intervals after exercise in MT, OT and OR groups. These data confirm a positive effect of moderate exercise on immune function and a decrease in susceptibility to viral infection by inducing Th1 cytokine profile shift. However, prolonged and overtraining exercise causes numerous changes in immunity that possibly reflects physiological stress and immune suppression.