The aim of this study is to investigate the effects of CYP11B2 gene polymorphisms with the adrenocorticotropic hormone (ACTH) and angiotensin II (Ang II) in Chinese patients with type 2 diabetes (T2DM) and hypertension (T2MH). A total of 457 T2DM patients were genotyped for the polymorphism of rs3802228 and rs1799998 using SNP-scan high-throughput technology. The levels of adrenocorticotropic hormone in peripheral blood and related biochemical indices including aldosterone, renin, and Angiotensin II were measured and analyzed in relation to CYP11B2 polymorphisms in T2DM patients. As we found that Compared with T2DM patients, ACTH levels were higher in the rs3802228 AA/AG and rs1799998 AA/AG genotype T2MH subgroups (P < 0.001, P = 0.001). However, the difference in ACTH levels between two identical genotypes of T2MH was not statistically significant compared with T2DM patients (P > 0.05), whereas both AA and AG genotype subgroups had different AngII levels (P < 0.001, P = 0.004), which were higher than those of T2DM patients, but with a decrease in ACTH levels compared with patients with a single AA or AG genotype. Logistic regression analyses indicated that there was no significant relationship between genotype and allele polymorphisms with T2MH progression after adjustment for confounders. As a conclusion, CYP11B2 gene polymorphism was not associated with susceptibility to hypertension in Chinese T2DM patients, but its association with ACTH and Ang II levels may be a risk factor for susceptibility to hypertension in Chinese T2DM patients.