Background: Diabetes mellitus is a major risk factor for cardiovascular disease and is associated with a proinflammatory and prothrombotic state. We investigated whether CD40 ligand (L) expression and platelet–monocyte aggregation are increased in patients with type 1 diabetes. Methods: Serum C-reactive protein (CRP) and soluble (s) CD40L concentrations, platelet surface CD40L expression and platelet–monocyte aggregates were measured in 22 patients with uncomplicated type 1 diabetes and 22 age- and sex-matched non-diabetic control subjects. Results: In comparison to controls, patients with type 1 diabetes had higher serum CRP concentrations (3.29 ± 0.9 mg/L versus 0.99 ± 0.2 mg/L, P = 0.01), serum sCD40L concentrations (10.0 ± 1.4 ng/mL versus 4.6 ± 0.6 ng/mL, P = 0.006), and platelet surface expression of CD40L (13.8 ± 0.9% versus 8.5 ± 1.1%, P < 0.001). Platelet–monocyte aggregates were also significantly elevated in type 1 diabetes (35.9 ± 3.3% versus 26.4 ± 2.9%, P = 0.005; n = 10). We also observed a significant correlation between plasma glucose and serum CRP ( r = 0.53, P = 0.01) as well as platelet–monocyte aggregates ( r = 0.69, P = 0.03). Conclusions: Type 1 diabetes is associated with increased CD40L expression and platelet–monocyte aggregation, which may contribute to the proinflammatory and prothrombotic state as well as the accelerated atherogenesis associated with this disorder.