Müller cell gliosis is a universal response in many retinal pathological conditions, including glaucoma.Accompanying the enhanced expression of glial fibrillary acidic protein (GFAP), the Kir K+ channel is downregulated in most, if not all, retinal diseases.The mechanisms underlying Müller cell gliosis and the downregulation of K+ currents are poorly understood.Here, we show that Müller cell Kir currents were reduced significantly and GFAP expression was increased in a rat chronic ocular hypertension (COH) model.The group Ⅰ mGluR agonist DHPG mimicked the COH-induced suppression of Kir currents, and this was selectively blocked by the mGluR5 antagonist MPEP.The intracellular Ca2+-dependent PLC/IP3-ryanodine/PKC signaling pathway mediated the DHPG effect.COH-induced changes in Müller cells were eliminated by injecting MPEP and were mimicked by an intravitreal injection of DHPG.Thus, mGluR5-mediated suppression of Kir currents contributed to retinal Müller cell gliosis in a rat COH model.