Background: Diabetic retinopathy (DR) is the most frequent ocular complication of diabetes mellitus and the leading cause of blindness in the working age population in developing countries. Objective: The aim of this study was to compare central macular thickness using optical coherence tomography (OCT) between Ranibizumab 0.5 mg monotherapy over Ranibizumab 0.5 mg combined with laser based on mean average change in best-corrected visual acuity (BCVA) over 6 months in diabetic macular edema (DME). Patients and methods: The study was carried out on forty eyes of patients aged 30-75 years old, with type 1 or 2 diabetes mellitus and have visual impairment due to DME. The patients were selected from the Outpatient Ophthalmology Clinic of Aswan University Hospital. Results: Both groups achieved improvement of visual acuity and reduction of the macular thickness but the effect was more pronounced and long lasting in the combined therapy group. Conclusion: The use of more than one line of treatment in combination for patients with diffuse DME could provide more sustained results with the need for less frequent injections and decreasing the recurrence or persistence rate of DME.