ABSTRACT: The study aimed to investigate the effect of limited fluid resuscitation on gene profiles of rat hepatic tissue. Limited fluid resuscitation can reduce mortality resulting from traumatic hemorrhagic shock. However, the protective mechanism of limited fluid resuscitation is not very clear. The rats were subjected to uncontrolled hemorrhagic shock and resuscitated with limited fluid resuscitation or aggressive fluid resuscitation. Following 5 h of resuscitation, hepatic RNA was isolated, and gene expression profiles were measured using a NimbleGen microarray. Gene ontology (GO) and pathway analyses were performed. Real-time reverse transcription polymerase chain reaction was used to verify the microarray findings. A total of 449 differentially expressed genes between aggressive fluid resuscitation and limited fluid resuscitation groups were found. The GO analysis of differential gene expression predicted a significant downregulation of response to stress, alcohol biosynthetic process, response to wounding, gluconeogenesis, hexose biosynthetic process, acute inflammatory response, inflammatory response, response to oxygen levels, glucose metabolic process, acute-phase response, and so forth, and upregulation of steroid biosynthetic process, sterol metabolic process, steroid metabolic process, alcohol metabolic process, lipid metabolic process, cholesterol metabolic process, glycogen catabolic process, glucan catabolic process, cellular polysaccharide catabolic process, monocarboxylic acid metabolic process, and so on. This study showed that limited fluid resuscitation can downregulate the expression of injury-associated differentially expressed genes and upregulate the expression of metabolism-associated differentially expressed genes, which may account for the attenuation of the deleterious effects and overall prosurvival effects of limited fluid resuscitation on uncontrolled hemorrhagic shock.