Radiation-induced brain injury involves acute, early delayed and late delayed damage based on the time-course and clinical manifestations. The acute symptoms are mostly transient and reversible, whereas the late delayed radiation-induced changes are progressive and irreversible. Therefore, evaluation of the organ-specific early response to ionizing radiation exposure is necessary for improving treatment strategies and minimizing possible damage at an early stage after radiation exposure. In the current study, the gas chromatography-mass spectrometry technique based on metabolomics coupled with metabolic correlation network was applied to investigate the early metabolic characterization of rat brain tissues following irradiation. Our findings showed that the metabolic response to irradiation was not just limited to the variations of individual metabolite levels, but also accompanied by alterations of network correlations among various metabolites. Metabolite clustering indicated that energy metabolism disorder and inflammation response were induced following radiation exposure. The correlation networks revealed that the strong positive correlations of differential metabolites were highly reduced and significant negative linkages were highlighted in irradiated groups even without statistical changes in metabolic levels. Our findings provided new insights into our understanding of the radiation-induced acute brain injury mechanism and clues as to the therapy target for clinical applications.