Purpose: To compare the efficacy of intravitreal (IV) ranibizumab (IVR) injection with IV dexamethasone implant (IVDEX) in treatment naive diabetic macular edema (DME) patients with inflammatory component. Materials and methods: Treatment naive DME eyes with subfoveal neurosensorial detachment (SND) and hyperreflective spots (HRS) were treated either three loading doses of IVR (18 eyes) or one dose of IVDEX (19 eyes). Central macular thickness (CMT), height of SND, the number of HRSs scattered on the individual retinal layers and photoreceptor integrity were assessed using spectral domain- optical coherence tomography scans over 3-months follow-up. Results: The mean change in best-corrected visual acuity (BCVA) was -0.11 +/- 0.08 logMAR in IVDEX group and -0.04 +/- 0.06 logMAR in IVR group at 1-month (p = 0.011). IVDEX group showed statistically significant more increase in BCVA compared to those receiving IVR injections at 2-months (p = 0.004) and 3-months (p = 0.017) visits. Compared to baseline, the number of total HRSs and the number of HRSs at each individual inner retinal layer significantly decreased in both groups at all follow-up visits. However, IVDEX group showed more decrease in the total number of HRSs at 2- and 3-months (p < 0.001 at 2-months, and p = 0.006 at 3-months) and in the mean number of HRSs located at inner nuclear layer-outer plexiform layer level (p = 0.016 at 1-month, p < 0.001 at 2-months, and p < 0.001 at 3-months). After treatment, the number of HRSs on the outer nuclear layer showed some non-significant increase in both groups. Conclusion: HRSs tended to migrate from inner retina to the outer retina in DME eyes by treatment. Dexamethasone seemed to be more effective option in such cases with inflammatory component.