Intraperitoneal injection of recombinant human interleukin-2(rhIL-2) inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer. Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation. The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups. Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2. However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours. LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively. Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma. These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models. Intraperitoneal injection of recombinant human interleukin-2 (rhIL-2) inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer. Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival, macrophage activation, and PI3K / Akt and JAK / STAT activation. The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups. Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2. However, protein expression was increased at 12 hours, but decreased again at 24 hours, with very low expression at 96 hours. LY294002 and AG490, which are inhibitors of the PI3K / Akt and JAK / STAT3 signal pathways, prevented upregulation of Akt and STAT3 protein expression in the retina, respect ivitly. Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma. These results suggest that intravitreal injection of rhIL-2 could induce the PI3K / Akt and JAK / STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.