AIM: To investigate whether the neurons containing γ-aminobutyric acid B receptor 1 subunit(GABABR1) in the hypothalamic paraventricular nucleus(PVN) are involved in the immuno-stimulating stress induced by lipopolysaccharide(LPS) in the rats. METHODS: LPS was intraperitoneally injected into rats to stimulate the immune system and same volume of normal saline was give in control group as well. Immunofluorescence double staining and laser scanning confocal microscopy was used to observe the expression of Fos and GABABR1 as well as the relationship between the two in the PVN. RESULTS: A large number of Fos and GABABR1 positive neurons were observed in the PVN. The number of Fos positive neurons was increased significantly after the LPS immuno-stimulating in contrast to control group. Fos/GABABR1 double-labeled neurons were mainly observed in the area of medial parvocellular subdivision close to lateral magnocellular subdivision. The proportion of Fos/GABABR1 double-labeled neurons to Fos or GABABR1 single positive neurons was 30% and 24% respectively. CONCLUSION: Some of GABABR1 positive neurons in the PVN participate in immuno-stimulating stress and they may play important role in regulation of hypothalamic-pituitary-adrenocortical or stress axis.