Abstract Background VEGF has an essential role in initiating wound and inflammation-related neovascularization. Several studies have demonstrated that VEGF is an important mediator of blood– retinal-barrier breakdown, leading to fluid leakage below the macula and inducing the development of macular edema and choroidal neovascular membranes. Anti-VEGF agents interfere with its receptor binding, thus inhibiting VEGF’s signal, which results in inhibition of abnormal blood vessel formation and decreasing vascular permeability. Aim of the Work This study aimed is to report early changes in the corneal endothelial cell density (ECD) and morphology in patients undergoing intravitreal anti-VEGF injections (ranibizumab) for treatment of macular edema. Patients and Methods This prospective study included 22 eyes of 22 DME patients indicated for IVI of Ranibizumab, with mean age 57.1±7.4 years, ranging from 42.0 years to 70.0 years. The majority of them were females (77.3%). Results Cell density (endothelial cell count) at baseline (2601.8±220.0) didn’t show statistically significant difference than that at one month (2598.9±198.1) after IVI. Coefficient variant was not significantly changed at month-1 as compared to baseline. Coefficient variant at baseline was 29.8±4.0, ranging from 22.0 to 39.0. and at one month was 31.3±5.4, ranging from 21.0 to 48.0. Hexagonal cells (HEX) were not significantly changed at one month as compared to baseline. Hexagonal cells at baseline were 68.9±3.2, ranging from 63.0 to 75.0 and after one month, it was 67.8±4.1, ranging from 60.0 to 76.0. Pachymetry was not significantly changed at one month as compared to baseline. The corneal thickness (pachymetry) at baseline was 538.8±40.1 ranging from 448.0–587.0 to 447.0–597.0. after one month of IV ranibizumab it was 536.3±42.1 0.183. Conclusion A single IV injection of Ranibizumab in phakic and otherwise normal eyes with DME showed no change in ECD and pachymetry but a statistically non-significant increase in CV and decrease in HEX 1-month after injection.