Background: Ranibizumab (RBZ) is a recombinant humanized antibody fragment that is active against all isoforms of VEGF-A, the most important players in the pathogenesis of diabetic macular edema (DME). Subthreshold 577 nm micropulse yellow laser (SMYL) was designed to fire a series of millisecond laser pulses in spaced-out intervals, reducing thermal retinal damage and allowing selective treatment to the RPE, preserving retina and reduced inflammation. Low-energy micropulse laser treatment allows tissue to cool between pulses to limit and confine the therapeutic photothermal effect within the tissue directly targeted by the laser. Objective: A prospective comparative study between ranibizumab monotherapy versus ranibizumab combined with adjuvant SMYL in treatment of DME. Patient and methods: A prospective randomized clinical study was done in military eye hospital. 120 eyes were presented by DME included in this study. 60 eyes treated by intravitreal RBZ (IVRBZ) monotherapy (RBZ group) and the other 60 eyes treated by IVRBZ with SMYL application (RBZ+SMYL group). Follow up of best corrected visual acuity (BCVA) and central macular thickness (CMT) for one year was done. Results: It was found that BCVA was 0.25 ± 0.10 among RZB group and 0.27 ± 0.11 among RZB+SMYL group after 12 months. CMT was 307.78 ± 34.45 µm among RZB group and 287.07 ± 31.5 µm among RZB+SMYL group after 12 months. Conclusion: Combined IVRBZ and SMYL are more effective in control of DME more than IVRBZ monotherapy.