The objective of this study was to alleviate the acidity of PLGA nanofiber degradation in vitro by introducing the basic amino acid Lysine (Lys) into the PLGA nanofibers. PLGA and PLGA/Lys composite nanofibers were prepared via electrospinning, and the morphology, thermodynamic and mechanical properties of these nanofibers were characterized by SEM, DSC and mechanical testing, respectively. Release profiles of the Lys from the PLGA-based composite nanofibers were thereafter determined. Morphology of the degraded nanofibers and pH of the PBS solution, in which PLGA and PLGA/Lys nanofibrous mats were soaked at 37 degrees C for up to eight weeks,were assessed to detect the degradation behavior. Finally, cytotoxicity was performed by culturing vascular smooth muscle cells (SMCs) with fluid containing degraded product after eight weeks of degradation. It was found that the release kinetics of Lys from the electrospun PLGA/Lys nanofibers was Lys content dependent. Incorporation of Lys enhanced the degradation process of PLGA and mitigated the decrease of PBS solution pH (acidity). PLGA nanofibers containing 2% Lys are capable of maintaining the pH value between 7.4 and 6.7. Proliferation of SMCs was hindered in the presence of acidic products. But the SMCs grew well in the solution containing degraded products and Lys.