Background: Recent studies by our group indicate that preconditioning, therapeutic hypothermia (TH) and TH combined with preconditioning improved long-term survival during resuscitation of hemorrhagic shock. The neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation associated with increased mortality in patients with severe hemorrhage shock. The aim of this study is to evaluate the effects of these three therapies on NLR level in rats with acute hemorrhagic shock. Methods and Results: In the preconditioning study, Sprague Dawley rats (both genders) were randomized to preconditioning (n=26) or control group (n=27); in the hypothermia study, rats were randomized to TH (n=16) or control group (n=15); in a combination study, rats were randomized to TH plus preconditioning (n=11) or control group (n=10). Rats were anesthetized with intraperitoneal Ketamine and xylazine. After heparinizing, hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure (MBP) of 30 mmHg for 30 minutes and then shed blood was reinfused. Preconditioning was induced by 4 cycles of inflating small cuffs around the femoral arteries to 200 mmHg for 5 minutes, followed by 5-minute deflation of the cuffs prior to hemorrhagic shock. TH started at 5 minutes after MBP reached 30 mmHg. Core temperature was maintained at ~32 °C until blood volume was fully restored. In the control group, body temperature was maintained at ~ 37°C. Arterial blood samples were collected 1 hour after resuscitation. The NLR is an easily accessible biomarker, which is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The NLR was significantly lower in TH group (0.20 ± 0.02) compared with the control group (0.32 ± 0.03; p=0.003). Similarly, the NLR level was significantly decreased in TH plus preconditioning group (0.19 ± 0.02) versus the control group (0.33 ± 0.02; p= 0.001). There was no difference in NLR level between the preconditioning group (0.41 ± 0.04) and the control group (0.41 ± 0.04; p=0.984). Conclusions: NLR is widely recognized inflammation marker associated with poor prognosis in severe hemorrhagic shock. TH alone and TH combined with preconditioning blunt the inflammation by decreasing the NLR level in experimental hemorrhagic shock.