In this study, chitosan-atorvastatin (Chi-AT) conjugate was immobilized onto the surfaces of titanium substrates to reduce inflammation responses and improve cytocompatibility. Polydopamine film was initially formed onto the titanium surfaces as the intermediate layer for the successful immobilization of Chi-AT, which was confirmed by scanning electron microscopy, X-ray photoelectron spectroscopy, and contact angle measurements, respectively. Endothelial cells grown onto Chi-AT immobilized titanium substrates displayed significantly higher (p < 0.01) cell viability and statistically lower (p < 0.01) lactate dehydrogenase production than those of native titanium substrates (control) after culture for 4 days and 7 days, respectively. Furthermore, macrophages cells cultured onto Chi-AT immobilized titanium substrates demonstrated significantly lower (p < 0.01) production levels of nitric oxide, acid phosphatase, reactive oxygen species, pro-inflammatory cytokines of tumor necrosis factor α, and interleukin-1 β than those of controls. All results indicated that the immobilization of Chi-AT conjugate onto titanium substrates was beneficial for improving their cytocompatibility and inhibiting pro-inflammatory responses. The study thus presents an alternative to fabricate bio-functionalized titanium-based implants for further clinical application. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.