Central retinal artery occlusion (CRAO) is one of the serious ophthalmological emergencies with poor visual prognosis. Iloprost is a stable prostacyclin analogue and has prominent anti-edema, anti-inflammatory, vasodilatory, and antiagregant effects. The main objective of this work was to investigate iloprost as an alternative agent versus hyperbaric oxygen (HBO) in the treatment of CRAO. Twenty-eight healthy Wistar albino male rats were randomly assigned into control (n = 7, sham operation), HBO (n = 7), iloprost (n = 7), and sham groups (n = 7). CRAO model was created through optic nerve exploration and ligation. Full-thickness retina (FTR), outer nuclear layer (ONL), inner nuclear layer (INL) and ganglion cell layer (GCL) thickness were measured on Hematoxylin/Eosin (H&E) stained retinal sections and immunohistochemical analysis including terminal deoxynucleotidyl transferase-mediated biotindeoxyuridine triphosphate nick-end labeling (TUNEL) assay was performed to determine the apoptotic index (AI). AI values of HBO (0.204 ± 0.067) and iloprost (0.197 ± 0.052) groups were significantly lower than sham (0.487 ± 0.046) group (p < 0.001). Any significant difference was found between the HBO and iloprost groups in terms of AI (p = 0.514). A statistically significant increase in thickness of FTR, ONL, INL and GCL was detected in HBO, iloprost and sham groups compared to the control group (p = 0.002). FTR, ONL, INL and GCL thickness were significantly thinner in HBO and iloprost groups than in the sham group (p = 0.002). A significant lesser increase was observed in all the retinal layers thickness in iloprost group versus HBO group (p = 0.002) except for INL (p = 0.665). The study results demonstrated anti-edema, neuroprotective, and anti-apoptotic effects of iloprost quantitatively; thus, iloprost may be a beneficial alternative agent in the treatment of CRAO. Karaman, Ozkan, Yazir, Yardimoglu, Gok, Kara, Vural, Rencber, (2016). Comparison of hyperbaric oxygen versus iloprost treatment in an experimental rat central retinal artery occlusion model. Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2016 Nov;254(11):2209-2215. https://www.ncbi.nlm.nih.gov/pubmed/27480178