Purpose: To investigate the effect of calcium dobesilate on inner macular thickness measured with optical coherence tomography in the eyes with severe non-proliferative diabetic retinopathy (NPDR).Methods: The study participants were 28 patients (n = 28 eyes) who had severe NPDR without severe diabetic macular edema and who were followed up after treatment with calcium dobesilate for ≥ 3 months. Central macular thickness (CMT), total macular volume (TMV), and ganglion cell complex (GCC) at baseline and the 3 months follow-up were analyzed retrospectively. The matched patients with bilberry dried extract were selected and compared as a control group.Results: In the calcium dobesilate group, the CMT and TMV measured before and 3 months after treatment were 265.36 ± 16.31 µm, 8.72 ± 0.45 mm3 and 262.39 ± 15.13 µm, 8.67 ± 0.46 mm3, respectively. A significant decrease in observation time was observed p = 0.009, p = 0.010). GCC decreased from 106.31 ± 8.16 µm to 105.18 ± 7.53 µm p = 0.036), of which retinal nerve fiber layer decreased from 34.27 ± 3.96 µm to 33.93 ± 3.80 µm p = 0.219), and GCL from 39.47 ± 3.61 µm to 38.87 ± 3.217 µm p = 0.012), inner plexiform layer changed from 32.56 ± 2.24 µm to 32.39 ± 2.14 µm p = 0.211).Conclusions: In patients with severe NPDR, a decrease in inner retinal thickness was observed after 3 months of taking calcium dobesilate, and the ganglion cell layer showed a significant decrease in thickness.