The aim of this work is to evaluate the effect of Hyperbaric oxygen (HBO) therapy in diabetic macular edema (DME). Patients and Methods: In this study we selected 100 eyes of 50 patients having bilateral DME. Patients did not receive intravitreal injections or laser before the study. They had exposed to HBO according to the treatment protocol. Evaluation was done by measuring the macular thickness using Optical Coherent Tomography (OCT) and best corrected visual acuity (BCVA). Results: The LogMAR BCVA was improved from 0.96 ± 0.28 at baseline to 0.65 ± 0.27, 0.63 ± 0.19, 0.58 ± 0.25, 0.61 ± 0.21 and 0.62 ± 0.23 at 1, 2, 3, 6 and 12, respectively, with change of 0.31 (32.3%), 33 (34.4%), 0.38 (39.6%), 0.35 (36.5) and 0.34 (35.4%), at 1, 2, 3, 6 and 12, respectively, from the baseline. They all showed statistically significant difference in comparison to baseline. The CMT was decreased from 439.2 ± 144.5 µm at baseline to 375.6 ± 132.2 µm, 332.5 ± 129.7 µm, 289.4 ± 131.4 µm, 238.7 ± 142.5 µm and 273.8 ± 145.1 µm at 1, 2, 3, 6 and 12, respectively, with change of 63.6 µm (14.5%), 106.7 µm (24.3%), 149.8 µm (34.1%), 200.5 µm (45.7% and 165.4 µm (37.7%), at 1, 2, 3, 6 and 12, respectively, from the baseline. They all showed statistically significant difference in comparison to baseline. Conclusion: HBO is proved in this study that it was safe and effective in treatment of DME. However, more researches were recommended with extensive details to explore its efficacy especially in long-term follow-up periods