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Purpose: To evaluate the macular thickness changes in diabetic macular edema after meal. Methods: In this prospective case series, macular thicknesses of diabetic patients with clinically significant macular edema (CSME) were measured after 7 h of fasting and repeated 2 h after breakfast. Results: Thirty six eyes of 20 diabetic patients were evaluated. The mean central subfield thickness (CST) and maximum retinal thickness (MRT) significantly decreased after meal (mean change of −10.3 ± 14.3 μm and −13.1 ± 12.7 μm, respectively, both P < 0.001). A decrease in CST and MRT values was found in 23 (63.8%) and 28 (77.7%) eyes, respectively, and no eye had an increase in retinal thickness measurements. Significant correlation was found between CST and MRT change and fasting thickness measurements (P = 0.001 and P = 0.01, respectively) and intraretinal cystic spaces (P = 0.001 and P = 0.03, respectively). Mean MRT change was significantly higher in the presence of subretinal fluid (P = 0.01). Conclusion: Retinal thickness measurements may change after meal. So, fasting state of diabetic patient should be considered in measurement of macular thickness of patients with CSME.