Restenosis is the formation of new blockages at the site of angioplasty or stent placement. In order to avoid this, the suppression of smooth muscle cells near the implanted stent is required. the Akt1 protein is known to be responsible for the cellular proliferation and specific inhibition of Akt gene expression resulted in the retardation of cell growth. To achieve this, we developed new delivery technique of Akt1 siRNA nanoparticles from hyaluronic acid (HA) coated surface. For this purpose, the disulfide-crosslinked low molecular PEI, ssPEI, was used as a gene delivery carrier, because the disulfide bonds are stable in the oxidative extracellular environment but degrade rapidly in the reductive intracellular environment. In this study, the Akt1 siRNA showed efficient ionic interaction with ssPEI carrier, which was confirmed by polyacrylamide gel electrophoresis. Also, Akt1 siRNA / ssPEI nanoparticles, immobilized on the HA-coated surface, exhibited stable binding and localization to the HA-coated surface, followed by time-dependent sustained release for the intracellular uptake. The cellular viability on the nanoparticles-immobilized surface was assessed with A10 vascular smooth muscle cells and revealed that the immobilized Akt1 siRNA/ssPEI nanoparticles exhibited neglectable cytotoxicity against the adhering A10 cells. The transfection efficiency was quantified with the luciferase assay and the transgene expression of Akt1 silenced by delivered Akt1 siRNA was measured using RT PCR and western blot, demonstrating higher gene silencing efficiency when compared to other carriers. Akt1 siRNA nanoparticles coated on HA-stent was deployed in the balloon injured external iliac artery of the rabbit in vivo. It was shown that the Akt1 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis at the post-implantation.