Objective: Retinopathy of prematurity is becoming obvious with the improvement of neonatal ambulance. However there is still not a good treatment. The present study is to observe the effect of 17 beta-estradiol (E2) on oxygen-induced retinopathy (OIR), and explore the relationship between the changes of avascular area and malondialdehyde (MDA) in retina. Methods: Newborn oxygen-exposed mice underwent subcutaneous injections of different dose of E2 (0.1 μg, 1.0 μg, 10.0 μg ), tamoxifen or phosphate buffered saline (PBS; controls)everyday from post-natal day (p)7 to p17. At p17, retinal flat mounts were scored for the percentage of avascular/total retinal area, and pathological changes during revascularization. The MDA concentration in the retina was determined also. In the most efficacious E2 group (10.0 μg), 100.0 μg tamoxifen was also administered, and the percentage of capillary-free/total retinal area determined, and the retinal malondialdehyde concentration assayed. Results: The mean percentage of capillary-free area over total retinal area was 0(PBS, in room air), 34.197±1.301(PBS, in hyperoxia), 23.685±0.407 (0.1 μg E2), 14.648±0.355 (1.0 μg E2), 4.693±0.450 (10.0 μg E2) and 32.240±0.654 (10.0 μg E2 +100.0 μg tamoxifen). The difference was significant (F = 2778.759, P < 0.01), and the difference between any two groups were also significant (all P value were less than 0.01). The predilection of tufts and clusters during revascularization was mainly aggregated in zones 2 and 3, but the difference of retinal neovascular clusters and tufts in fourth zone among different groups were significant [clusters (F = 44.719, P < 0.01) vs tufts (F = 39.997,P < 0.01)]. The mean MDA concentration were 0.711±0.037(PBS, in room air), 2.084±0.066 (PBS, in hyperoxia), 1.829±0.091(0.1 μg E2), 1.152±0.067(1.0 μg E2), 0.796±0.027(10.0 μg E2), 1.988±0.049(10.0 μg E2 +100.0 μg tamoxifen) (F = 628.103, P < 0.01). The difference between any two groups were also significant (all P value were less than 0.05). The close relation between the percentage of avascular/total retinal area and MDA concentration was also verified (r = 0.981, P < 0.01). Conclusion: Oxidative stress responses play a pivotal role in OIR, by means of receptor pathway. E2 can alleviate oxidative stress reaction, and thus ameliorate the severity of oxygen induced retinopathy.