Objective: We tested the extent to which altered plasma adipokine levels may contribute to the increased carotid artery intima-media thickness (IMT) associated with type 2 diabetes mellitus and with male gender, independently of conventional cardiovascular risk factors, insulin resistance, and plasma C-reactive protein (CRP). Design: IMT (mean of three segments of both carotid arteries by ultrasonography), insulin resistance (homeostasis model assessment; HOMA(ir)), plasma CRP, lipids, adiponectin, leptin, resistin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 84 type 2 diabetic patients and 85 control subjects. Results: In diabetic patients, IMT (P < 0.001), mean arterial pressure (P < 0.001), HOMAir (P < 0.001), plasma CRP (P = 0.003), triglycerides (P = 0.037), leptin (P = 0.023), resistin (P = 0.003), and TNF-alpha (P = 0.003) levels were higher, whereas high-density lipoproteins (HDL) cholesterol (P < 0.001) and adiponectin (P < 0.001) levels were lower compared with control subjects. Plasma adiponectin (P < 0.001) and leptin (P < 0.001) were substantially lower in men than in women. IMT was positively and independently associated with age (P < 0.001), diabetes (P = 0.049), and male gender (P = 0.002) in a multivariate regression model, not including other variables. Further analyses showed that IMT was positively related to age (P < 0.001) and plasma triglycerides (P = 0.038) and negatively to adiponectin (P < 0.001), without independent effects of diabetes, gender, and HOMA(ir). Conclusions: Increased IMT in type 2 diabetes may in part be explained by lower plasma adiponectin and higher triglycerides, but not by leptin, resistin, and TNF-alpha. The gender effect on IMT is related to lower plasma adiponectin.