P>Aims Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose-response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. Methods Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was >= 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. Results Compared with non-smokers, those who had smoked 15-30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34-5.76, P < 0.01) and 3.20 (95% CI 1.74-5.86, P < 0.001) times more likely to develop proteinuria. The dose-response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects (P = 0.001) and in subgroups with relatively short duration of diabetes mellitus (P < 0.001), good blood pressure control (P = 0.001) and those of young age (P = 0.007). Conclusions The current study shows a clear dose-response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control.