The plasma technique has been widely used to modify the surfaces of materials. The purpose of this study was to evaluate the probability of controlling the prednisolone delivery velocity on a polylactic acid (PLA) surface modified by plasma surface treatment. Surface modification of PLA was performed at a low-pressure radio frequency under conditions of 100 W power, 50 mTorr chamber pressure, 100~200 sccm of flow rate, and Ar, O2, and CH4 gases. The plasma surface-modified PLA was characterized using scanning emission microscope, X-ray photoelectron spectroscopy (XPS), and contact angle measurements. In vitro evaluations were performed to determine cellular response, drug release behavior, and anti-inflammatory effects. The PLA surface morphology was changed to a porous structure (with a depth of approximately 100 μm) and the surface roughness was also significantly increased. The XPS results demonstrated higher oxygenized carbon contents than those in the non-treated PLA group. The prednisolone holding capacity increased and the release was relatively prolonged in the surface-modified PLA group compared to that in the non-treated PLA group. In addition, cell migration and proliferation significantly increased after PLA treatment alone. The activity of cytokines such as COX-2, TNF-α, IL-1β, and IL-6 were considerably reduced in the plasma-treated and prednisolone holding group. Taken together, surface-modified PLA by plasma can provide an alternative approach to conventional physicochemical approaches for sustained anti-inflammatory drug release.