OBJECTIVE—The relationship between cigarette smoking and renal dysfunction in diabetes has predominantly been documented in patients with type 1 diabetes. The aim of the present study was to explore the relationship between cigarette smoking and glomerular filtration rate (GFR) in a large cross-sectional study carried out in male subjects with type 2 diabetes. The role of metabolic syndrome in modulating this relationship was also investigated. RESEARCH DESIGN AND METHODS—One hundred fifty-eight current smokers and 158 never smokers with type 2 diabetes were consecutively recruited. Low GFR was defined as GFR <60 ml/min per 1.73 m2. RESULTS—The proportion of patients affected by low GFR was significantly higher in current smokers (20.9 vs. 12.0%, P = 0.03). The adjusted risk (odds ratio [OR]) of low GFR in current smokers was 2.20 (95% CI 1.14–4.26, P = 0.02) and markedly higher in patients from the first tertile of disease duration (4.27 [1.26–14.40], P = 0.02). When metabolic syndrome was added to the statistical model exploring the relationship between smoking and low GFR, the risk of low GFR showed a small change, although it did not become any more significant (1.84 [0.98–3.45], P = 0.06). Current smokers showed even higher free oxygen radical test unit values (560.0 ± 91.5 vs. 442.7 ± 87.2, P < 0.0001). CONCLUSIONS—In a large population of male patients with type 2 diabetes, the risk of low GFR is markedly enhanced by smoking and is at least partially mediated by metabolic syndrome.