Objective To investigate the effect of high-dose systemic steroids on retinal tissues and the effectiveness of ozone (O-3) therapy. Methods Twenty-four New Zealand white rabbits were divided into three groups of eight. Group 1 was accepted as the control group, Group 2 received intramuscular 20 mg/kg methylprednisolone acetate and Group 3 received 14 sessions of ozone treatment in addition to methylprednisolone acetate. The subjects were sacrificed on the 30(th)day. Retinal tissues were removed. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) levels were evaluated for tissue biochemistry and serum ischaemic modified albumin (IMA), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels were evaluated with the ELISA method. Haematoxylin-eosin staining and TUNEL evaluation for apoptosis were evaluated as histopathological methods. Results In the treatment group, antioxidant parameters of TAS, SOD and CAT were higher, oxidative and ischaemic parameters of MDA, TOS and IMA were lower, inflammatory parameters of IL-6 and TNF-alpha were lower, retinal thickness was better and apoptosis amount was lower. Conclusion Apoptosis increases in retinal tissues due to high dose systemic steroid administration and the retina becomes thinner. With biochemical examination, oxidation parameters increased while antioxidant parameters decreased. Both histopathological and biochemical parameters improved significantly with ozone treatment.