OBJECTIVE This study is designed to determine the effects of delayed fluid resuscitation on the hemodynamic changes and cytokine responses in a rat model of hemorrhagic shock. METHODS Wistar male rats (n=40; 8/group) were subjected to a volume-controlled hemorrhagic shock for 30 minutes and received lactated Ringer's solution resuscitation as follows: (1) immediate resuscitation, (2) delayed resuscitation begun 30 minutes after hemorrhage (delayed resuscitation 30), (3) delayed resuscitation begun 45 minutes after hemorrhage (delayed resuscitation 45), (4) delayed resuscitation begun 60 minutes after hemorrhage (delayed resuscitation 60), or (5) unresuscitated group, induction of hemorrhagic shock without resuscitation. Hemodynamic parameters were recorded and blood samples were collected at 0 minutes and at 30, 90, 150, 210, 270, and 330 minutes after hemorrhage for plasma levels of interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNF-alpha). Repeated-measurement analysis of variance was used for within- and between-groups comparisons. RESULTS Final mean blood pressure, serum levels of lactate, and hematocrit levels after immediate resuscitation were not different from those in the delayed resuscitation groups. Comparing with the unresuscitated group, TNF-alpha and IL-6 concentrations were significantly higher, whereas IL-10 concentrations were significantly lower in the 4 resuscitation groups. Circulating concentrations of IL-6 were significantly higher in the delayed resuscitation 45 (P<.001) and delayed resuscitation 60 (P<.001) groups. Circulating concentrations of TNF-alpha and IL-10 in the 4 resuscitation groups were comparable throughout the experimental period. CONCLUSIONS Delayed fluid resuscitation in hemorrhagic shock induces increased production of proinflammatory cytokines, and the release of cytokine was correlated with the time delayed for resuscitation.