Background To investigate the distribution of NADPH oxidase subunit p22phox gene C242T polymorphisms in T2DM patients and analyze the association of NADPH oxidase subunit p22phox gene C242T polymorphisms with vascular complications in diabetic patients. Methods We analyzed 273 patients with T2DM; these were divided into four groups: a normal IMT group, a thickened IMT group, a non-carotid atherosclerotic plaque group and a carotid atherosclerotic plaque group. Of the 273 patients, there were 186 cases of diabetic nephropathy (DN) and 212 cases of diabetic retinopathy (DR). The patients in each group were genotyped for NADPH oxidase subunit p22phox by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). After that, the DN and DR Patients were divided into 2 groups: CC genotype and the CT + TT genotype, respectively. Then, maximal systolic velocity (Vmax), minimal diastolic velocity (Vmin), mean velocity (Vmean), time velocity integral (TVI), resistance index (RI) and Pulse index (PI) were measured by Doppler ultrasound in the left renal artery (LRA) of DN patients and the central retinal artery (CRA) of DR patients. Results There was a significant difference between the normal IMT group and the thickened IMT group (P < 0.05) with regards to NADPH oxidase subunit p22phox gene C242T polymorphism. There was also a significant difference between the non-carotid atherosclerotic plaque group and thecarotid atherosclerotic plaque group (P<0.05) with regards to NADPH oxidase subunit p22phox gene C242T polymorphism. Further analysis showed that CRA Vmax, Vmin, VTI decreased, PI and RI increased in CC genotype DR patients, which were significantly different from those in CT+TT genotype DR patients. CC genotype DN patients showed the same results as CT+TT genotype DN patients (P<0.05, P<0.001). Conclusion The polymorphism of NADPH oxidase subunit p22phox gene is associated with carotid atherosclerosis in patients with T2DM, and can lead to the occurrence of DR and DN by affecting the hemodynamics of CRA and RA. Monitoring vascular conditions in patients with T2DM by CDUS can provide effective early warning information for patients to prevent vascular complications.