Background: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes with the potential to cause severe vision loss and blindness and a devastating effect on quality of life. Objective: Discuss the macular ganglion cell and retinal nerve fiber layer (RNFL) changes after laser treatment as a management of diabetic retinopathy. Patients and Methods: This study was carried out on 55 eyes of 35 patients designed as a prospective, interventional case series at Sohag Ophthalmic Diagnostic Laser Unit between January 2016 and March 2017. A complete ophthalmologic examination was performed, including best-corrected visual acuity (BCVA) using the ETDRS charts, intraocular pressure (IOP) measurement, slit-lamp biomicroscopic examination, fundus examination, fluorescein angiography, and 3D optical coherence tomography (OCT) 2000. Results: The value of RNFL (superior and total) in the GRID group is more than in the pan-retinal photocoagulation (PRP) group which increased at 1 month post laser (not significant) then significantly decreased at 6 month follow up. The value of RNFL (inferior) in the GRID group is more than in the PRP group which significantly increased at 1 month post laser then decreased at 6 month follow up table 4. Conclusion: Significant ganglion cell (GC) and RNLF decrease at the sixth month of follow-up can be attributed to axonal loss secondary to direct or indirect effects of PRP treatment. SD OCT is a very valuable tool to document the RNFL thickness changes following the argon laser photocoagulation.