The aim of the present study was to investigate the expression of leukemia inhibitory factor (LIF) and its downstream signaling pathways in the rat retina following acute ocular hypertension. The intraocular pressure of the rats was elevated to 110 mmHg for 1 h by infusing the anterior chamber with normal saline. The retinal tissues were obtained 12 h, 24 h, and 2, 3 and 7 days after termination of the ocular hypertension. Hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to assess the morphological changes and the apoptosis of retinal cells, respectively. Quantification of the retinal ganglion cells (RGCs) was performed using fluorogold retrograde (FG) staining. The expression levels of LIF, LIF receptor (LIFR), signal transducers and activators of transcription 3 (STAT3), phosphorylated STAT3 (P‑STAT3), Akt, phosphorylated‑Akt (P‑Akt), extracellular signal‑regulated kinase (ERK) and phosphorylated ERK (P‑ERK) were determined at different time‑points following acute ocular hypertension using western blot analysis. Reverse transcription‑quantitative polymerase chain reaction was performned to detect the mRNA expression levels of LIF and LIFR. The results revealed that 12 h, 24 h, 2, 3 and 7 days after reperfusion, the thickness of the inner nuclear layer and the inner plexiform layer was decreased, with a significant reduction in the number of RGCs, as determined using TUNEL and FG staining. The expression levels of LIF and LIFR were increased following acute ocular hypertension. At 12 h post‑retinal reperfusion, the expression levels of P‑STAT3 and P‑Akt were significantly upregulated, while the expression of P‑ERK was decreased. The changes in the expression levels of LIF and LIFR suggested that LIF may be important in the process of degeneration/protection following retinal ischemia induced by acute ocular hypertension, via activation of the Janus kinase/STAT and Akt signaling pathways.