Aims To investigate the effects of glycaemic control on insulin sensitivity and serum concentrations of soluble vascular cell adhesion molecule (sVCAM)-1 and E-selectin (sE-selectin) in patients with Type 2 diabetes mellitus. To examine whether reductions in serum adhesion molecule levels correlate with improvement in insulin resistance. Methods A total of 54 patients with Type 2 diabetes were treated for 4 weeks with either diet alone, sulphonylurea or insulin. Fasting glucose, insulin sensitivity, lipids, sVCAM-1, and sE-selectin levels were measured before and after treatment. Results All treatment modalities successfully corrected hyperglycemia. Reductions in blood glucose levels resulted in improvement in insulin sensitivity (diet K-ITT 2.40 +/- 0.26-3.09 +/-0.36, P < 0.01; sulphonylurea 2.24 <plus/minus> 0.16-2.94 +/- 0.18, P < 0.01; insulin 1.68 <plus/minus> 0.27-2.16 +/- 0.22%/min, P < 0.05), and decrease in sE-selectin levels (diet 88.4 <plus/minus> 14.9-66.2 +/- 10.8, P < 0.05; sulphonylurea 85.1 <plus/minus> 11.6-59.8 +/- 7.8, P < 0.01; insulin 84.4 <plus/minus> 8.7-66.8 +/- 7.4 ng/ml, P < 0.01), but no change in sVCAM-1 levels. There was a significant correlation between the degree of decrease in SE-selectin levels and improvement insulin sensitivity (r = -0.38, P < 0.01). Conclusions Correction of hyperglycaemia, independent of treatment modality, resulted in improvement of insulin resistance and decrease in sE-selectin levels. These changes might, in part, contribute to reduce the risk of diabetic microvascular and macrovascular complications in patients with Type 2 diabetes mellitus.