Abstract Background: Anti-VEGF agents interfere with receptor binding, thus inhibiting VEGF's signal, which results in inhi-bition of abnormal blood vessel formation and decreased vas-cular permeability. Anti-VEGFs have significant roles in the treatment of many retinal diseases as age related macular de-generation, myopic choroidal neovascularization, proliferative diabetic retinopathy, diabetic macular edema and retinal vein occlusion. Aim of Study: To evaluate changes in macular vessel den-sity following first dose of intravitreal anti-VEGF injection of ranibizumab (Lucentis®) in patients with diabetic macular ede-ma (DME). Patients and Methods: This prospective study included 44 eyes of 44 DME patients indicated for IVI of Ranibizumab, with mean age 50.98±6.27 years, ranging from 41.0 years to 60.0 years. The majority of them were males (68.2%). Results: Vessel density (central subfield) at baseline (20.29 ±1.89) didn't show statistically significant difference than that at one month (20.09±2.4) but showed a highly significant differ-ence at two months (19.73±2.49) after IVI. Vessel density (av-erage of the four parafoveal sub fields) at baseline (44.98±2.6) didn't show statistically significant difference than that at one month (44.8±2.21) but showed a highly significant difference at two months (44.14±2.2) after IVI. Conclusion: A single IV injection of Ranibizumab in eyes with DME showed non significant vascular density changes after one month of injection in both central and paraoveal sub-fileds but a statistically significant decrease in vascular density 2 months after injection.