Objective To investigate whether angiotensinogen (AGT) gene M235T variant is associated with non insulin dependent diabetes mellitus without nephropathy (DN -), and diabetic nephropathy (DN +) in Chinese non insulin dependent diabetes mellitus (NIDDM) Methods The subjects in DN + group, DN - group and control group were well matched with sex, age and duration of disease, and the two case groups were divided into two subgroups as with and without hypertension respectively The M235T polymorphism of AGT gene of 84 cases with DN -, 96 patients with DN + and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) analysis of the region of the variant, i e M235T polymorphism Results The increased frequencies of T allele (0 82) and TT genotype (0 70) were observed in 96 subjects with DN + as compared with 98 control subjects (0 63 and 0 43, respectively, P =0 003, P =0 0004) The odds ratio associated with TT genotype was 3 47 (95%CI: 1 51-7 94; P =0 0033) for diabetic nephropathy in analysis adjusted for several risk factors of diabetic nephropathy, such as body mass index, systolic and diastolic blood pressure, serum cholesterol, low density lipoprotein and high density lipoprotein Subgroup analysis of the 67 patients in DN + group with hypertension revealed similar distributions of M235T genotypes and alleles to those in the DN + without hypertension subgroup There was no difference in allele and genotype distribution between 84 DN - patients and the controls Similarly, frequencies of the AGT M235T genotype and allele were not different between two DN - subgroups Conclusions AGT gene M235T polymorphism is associated with diabetic nephropathy in NIDDM TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese NIDDM patients