Studies indicate that environmental exposure to lead is associated with reduced renal function. Whether lead affects progressive diabetic nephropathy is unclear. Eighty-seven patients with type II diabetes and diabetic nephropathy (serum creatinine of 1.5–3.9 mg/dl) with normal body lead burden and no lead exposure history were observed over a 12-month period. Thirty subjects with high normal body lead burdens (80–600 µg) were randomly assigned to a chelation and control group. For 3 months, the 15 chelation-group patients underwent lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly until body lead burden fell <µ60 g, and the 15 control group subjects received a weekly placebo. During the following 12 months, renal function was regularly assessed at 3-month intervals. The primary outcome was an elevation of serum creatinine to 1.5 times baseline value during the observation period. A secondary outcome was temporal changes in renal function following chelation therapy. Twenty-six patients achieved the primary outcome. Basal blood lead levels and body lead burden were the most important risk factors in predicting progressive diabetic nephropathy. Following chelation, the rates of decline in glomerular filtration rates in the chelation group and the control group, respectively, were ±5.05.7 ml and ±11.87.0 ml/min/year/1.73 m2 of body surface area (P=0.0084) during follow-up, although both groups had similar rates of progression of renal function during the 12-month observation period. We concluded that low-level environmental lead exposure accelerates progressive diabetic nephropathy and lead-chelation therapy can decrease its rate of progression.