The present study was designed to gain insight into the effects of s-limonene on the brain after 1-wk administration. For this purpose, neurotransmitters such as dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamic acid (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC-ECD and amino acid analyzer after 1-wk administration of s-limonene of different concentrations (0, 5, 25, 50 mg/kg). Significant changes, such as GABA, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time, basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of s-limonene was evaluated by corticosterone. Considering the increment of GABA and the changes of other neurotransmitters, anti-stress effects after 1-wk administration were observed. The experimental results showed that s-limonene could inhibit HPA activity under physical stress and this anti-stress effect of s-limonene may act through the GABA(A) receptor.