Investigation of the mechanisms underlying retinal photodamage occurring during vitreoretinal interventions is a topical issue of ophtalmology. The study aimed to assess the effect of endoillumination of varying intensity and duration on alteration of oxidative processes in rabbit blood. The experiment involved 16 rabbits, with their retinas exposed to endoillumination of different duration (30 and 60 min) and intensity (8 and 16 cd/m²). Blood samples were collected from the rabbits’ ear vein before and after light exposure. Whole blood and serum biochemiluminescence was measured in order to assess oxidative processes. The data were analyzed using the Mann–Whitney U-test, and the results were considered significant at p ≤ 0.05. A 30-minute light exposure resulted in a significant increase in whole blood biochemiluminescence: 1.5-fold at the intensity of 8 cd/m² and 2.5-fold at the intensity of 16 cd/m² relative to control values (p < 0.05), indicating enhanced reactive oxygen species generation by blood cells. In contrast, a significant decrease in serum biochemiluminescence was revealed: 1.2-fold at the intensity of 8 cd/m² and 2-fold at the intensity of 16 cd/m² compared to control (p < 0.05) , which likely indicates a compensatory increase in antioxidant activity in response to hyperactivation of free radical processes. With the 60-minute exposure, the changes in biochemiluminescence were more pronounced: 3- and 7-fold increase in whole blood biochemiluminescence and 2- and 3-fold decrease in serum biochemiluminescence, respectively. Thus, intense light exposure resulted in the oxidative process alterations determined by the intensity and duration of exposure.