Trace elements are essential for the proper functioning of proteins, enzymes, and transcriptional factors. However, toxic metals will compete with essential trace elements, and damage enzymatic activities and various physiological functions. We aimed to investigate the status of serum essential trace elements and toxic metals in Chinese diabetic retinopathy (DR) patients, and to analyze their associations.This retrospective study included 33 normal subjects (normal group), 44 type 2 diabetes mellitus (T2D) patients with DR (DR group), and 58 T2D patients without DR (diabetes mellitus [DM] group). Serum levels of zinc (Zn), manganese (Mn), cadmium (Cd), and cesium (Cs), were measured for all participants using inductively coupled plasma-mass spectrometry.The serum concentrations of Mn (0.0226 μg/L) and Zn (98.162 μg/L) were significantly lower in DR group, compared with both the DM group and normal group (P < 0.05). In contrast, the serum levels of Cs (0.0354 μg/L) and Cd (0.0149 μg/L) were significantly higher in DR group, compared with the normal group (Cs: z = 3.136, P = .002; Cd: z = 3.766, P < .0001). Similarly, the serum Cs level in the DM group was 0.0323 μg/L, which was significantly higher than that in the normal group (0.0167 μg/L, z = 2.692, P = .007). Moreover, the area under the receiver-operating characteristic curve values of Mn (0.753 [95% confidence interval, CI 0.635-0.872, P = .002]), and Cd (0.797 [95% CI 0.643-0.952, P = .003]) were significantly greater than those of Zn and Cs, for DR identification.Our results suggest that deficient essential trace elements and accumulated toxic metals were highly associated with the presence of DR.