Microvessels within neoatherosclerosis are associated with vulnerability and increase from the early to the very late phase after drug-eluting stent implantation. Microbubble contrast agents have been suggested to enhance tissue microvasculature for optical coherence tomography (OCT) imaging. The present study investigated whether OCT signal intensity of neointima within stented segments was enhanced after intracoronary administration of microbubble contrast agents. A total of 40 patients who underwent follow-up coronary angiography after drug-eluting stent implantation were enrolled. At the time of follow-up coronary angiography, OCT images of the stented segments were recorded before and after intracoronary administration of microbubble contrast agents. Mean OCT signal intensity of neointima after microbubble administration significantly increased [95.5 (85.7, 106.2) vs. 96.5 (88.7, 109.9), p = 0.001]. Multivariate analysis demonstrated the relationship between diabetes and greater neointima enhancement. The change in the OCT signal intensity of neointima following microbubble administration tended to be higher in diabetic patients than in non-diabetic patients [4.6 (0.6, 8.5) vs. 1.4 (− 1.1, 3.0), p = 0.05]. These findings suggest that this methodology may allow identification of neovascularization in neointima and evaluation of vulnerability of neoatherosclerosis. Microvessels in neointima may be a future target of pharmacological and interventional innovations for preventing stent failure.