Background: We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design: This was a parallel, two-arm, single-centre trial. Methods: Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108) or a low-fat diet (n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results: At the EOT, both the CD34(+)KDR(+) and CD34(+)KDR(+)CD133(+) counts had increased with the Mediterranean diet compared with the low-fat diet (p< 0.05 for both). At the EOT evaluation, there was a significant (p = 0.024) difference of P= 0.025mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) (p = 0.032 for both). Changes in the CIMTwere inversely correlated with the changes in EPC levels (CD34(+)KDR(+), r = - 0.24, p = 0.020; CD34(+)KDR(+)CD133(+), r = - 0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion: Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.