Aim To observe the thickness variation of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) in type 2 diabetes mellitus (T2DM) patients. To analyze the correlation of retinal neural structure parameters and microcirculation parameters. Methods This was a cross-sectional retrospective study including 45 T2DM patients (71 eyes) and 36 healthy controls (68 eyes). The optical coherence tomography angiography (OCTA) was used to examine GCC thickness, RNFL thickness, microvascular density of retinal superior capillary plexus, retinal deep capillary plexus and choroidal capillary plexus. Then the RNFL and GCC thickness changes were observed in the diabetic retinopathy (DR) patients of different stages, furthermore, the correlation was analyzed between these parameters and microvascular density. Results Compared with the control group, the focal loss volume (FLV, P＝0.00) and global loss volume (GLV, P＝0.00) of GCC thickness increased significantly in NDR group (DM patients without DR), so FLV and GLV might be the potential sensitive parameters to assess early loss of retinal ganglion cell (RGC) in NDR patients. Compared with the control group, the RNFL thickness decreased initially in the inferior and nasal quadrant in the patients with mild non-proliferative DR (NPDR) and moderate NPDR (P＝0.00), implying the more susceptibility regions for RNFL loss. In the severe NPDR group, the nasal RNFL thickness were still thinner (P＝0.00), whereas the inferior and temporal RNFL thickness went up significantly, compared with the control group (P＝0.00). In the PDR group, RNFL and GCC thickness in most regions were thicker than the control group, which might be relevant to retina thickening caused by the edema of retina. This might be supported by the positive correlation between the GCC/RNFL thickness and the retinal thickness revealed by the Spearman correlation analysis. In addition, the GCC and RNFL thickness were negatively correlated with retinal superficial capillary plexus(SCP) density, the deep capillary plexus (DCP) density and choroidal capillary plexus (CCP) density. Conclusion Local loss of GCC occurred in advance of the presence of DR, FLV and GLV in GCC thickness might be the potential sensitive parameters to assess early loss of RGC. With the development and progress of DR, the RNFL thickness tends to drop down influentially, then goes up finally. Therefore, further prospective and longitudinal clinical researches are needed.