Purpose: To investigate the relationship between intraocular pressure (IOP) and GABA receptors within the arcuate nucleus (ARC). Methods: In the chronic high IOP rat model, ibotenic acid (IBO) was injected to induce impairment of the ARC, and IOP was measured at the 0, 1, 2, 3, and 4 week time points with a Tono-Pen. To assess the expression of GABA-A/B receptors within the ARC under persistent high IOP, we performed immunofluorescence (IF) and immunohistochemical (IHC) staining at 2 weeks and 4 weeks. Furthermore, we treated the ARC with GABA-A/B receptor antagonists separately, and IOP was evaluated, as well as retinal ganglion cell apoptosis in the chronic high IOP rat model. In the following induced high IOP animal model, the expression of GABA-A/B receptors within the ARC was evaluated in DBA/2J mice which developed progressive eye abnormalities spontaneously that closely mimic human hereditary glaucoma. Results: Compared with the control group, statistically significant downregulation of IOP was noted due to the IBO injection into the ARC at the 2, 3, and 4 week time points (p<0.05). Persistent high IOP elicited increased expression of the GABA-A/B receptors in the ARC compared with the control group (p<0.01). In addition, treatment with GABA-A/B receptor antagonists separately caused a decrease in the IOP, along with reduced retinal ganglion cell apoptosis (p<0.01). In the DBA/2J mice, the expression of the GABA receptors was statistically significantly increased (p<0.01). Conclusions: GABA-A/B receptors in the ARC may be involved in regulation of IOP, and pathologically high IOP affects the expression of GABA-A/B receptors in the ARC.