Objective To detect which neurons participate in the synaptic plasticity in rat retina following acute high intraocular pressure (HIOP).Methods The acute HIOP model of SD rats was established by increasing the anterior chamber pressure of left eyes via a normal saline perfusion system until b wave of flash electroretinogragh (fERG) disappeared and maintained for 60 min.All right eyes served as normal control.The animals were sacrificed respectively on 2 h, 6 h, 12 h, 1 d, 3 d, 7 d and 14 d following operation.The serial frozen sectioned retinae were carried out with synaptophysin (SYN) immunohistochemistry.Double labeling of immunofluorescence technique was used to detect the co-expression SYN and specific markers of different retinal neurons.Results SYN up-regulated transiently 2 h following HIOP, then gradually reduced, and at 14 d gradually recovered.Compared to control, distribution of SYN was broadened in the outer plexiform layer (OPL) and extended to the inner part of the outer nuclear layer (ONL) following HIOP, while reverted to normal pattern at 14 d.The number of Paravalbumin positive amacrine cells in the inner nuclear layer (INL) was decreased following HIOP.However, the number of PKC-α-positive bipolar cells, Calbindin-expressing horizontal cells and rhodopsin-expressing rod photoreceptor cell remained unchanged significantly.PKC-α showed substantial co-localization with SYN in the inner part of OPL and inner plexiform layer (IPL).Rhodopsin showed co-localization with SYN in the OPL and the inner part of ONL after HIOP, and especially at 7 d.Paravalbumin showed co-localization with SYN in the IPL at the early stage after injury.Calbindin showed no co-localization with SYN except 7 d in the OPL.Conclusion There was synaptic plasticity in rat retina after acute HIOP which presented as expression upregulation and widened distribution of presynaptic functional protein in the OPL and ONL and degeneration in the IPL.Bipolar cells, rod photoreceptor cells, amacrine cells and horizontal cells may participate in the changes of synaptic plasticity.