Abstract: Objective To investigate the association of the PAI 1 promoter 4G/5G polymorphism and diabetic nephropathy in type 2 diabetes mellitus of North China.Methods The 4G/5G allele polymorphism in the PAI 1 gene promoter region were genetyped by allele specific PCR in 143 type 2 diabetic patients who had diabetes for over 10 years and 85 normal controls.The activity of PAI 1 was assayed by a chromogenic substrate method.Results Patients with type 2 diabetic nephropathy had a higher frequency of PAI 1 4G/4G genotype (39%) and 4G allele (60.5%) than those without nephropathy (33% and 56.5%),though not significantly ( P >0.05).The plasma PAI 1 activity in the diabeties with nephropathy was higher than that in the subjects without nephropathy ( P <0.05).PAI 1 activity was significantly higher in 4G allele homozygous than those in 4G/5G heterozygous and 5G homozygous ( P <0.005).Conclusion Elevated plasma PAI 1 activity is a risk factor for diabetic nephropathy.The presence of the 4G allele of PAI 1 gene was associated with a higher level of PAI 1 activity,and may involved in the generation of diabetic nephropathy.