PURPOSE: Central subfoveal thickness measurement is used in a large number of clinical trials to monitor the progression and treatment response of diabetic macular edema (DME) in patients of diabetic retinopathy (DR). Several studies have been carried out to investigate various factors affecting the central subfoveal thickness in order to minimize errors in the testing. We planned a study to investigate the effect of meals on central macular thickness (CMT) in patients with DME and compare that with nondiabetic patients. METHODS: In this observational study, 50 patients of diabetes with DME and 50 normal controls were included. Macular thickness was measured after overnight fasting and 2 h postprandial for both the groups. Any changes in morphology and CMT were evaluated. RESULTS: Each group had 22 females and 28 males with a mean age of 60.6 ± 6.6 in the diabetic group and of 49.66 ± 11.13 in the control group. Reduction in the CMT was noticed after the meals (mean: -9.78 ± 12.77 μm; < 0.001) in those with DME as compared to the control group. This was more prominent in those who had intraretinal cystic spaces (17.14 ± 10.33 μm) and neurosensory detachment (66 µ). Patients with high blood sugar levels had higher CMT and a greater reduction in thickness was noticed in them postprandially ( = 0.414; = 0.0028). CONCLUSION: The CMT values in patients with DME are significantly affected by meals. Hence, an attempt should be made to measure CMT during the fasting state for more accurate results.