Polymer scaffolds play an important role in three dimensional (3-D) cell culture and tissue engineering. To best mimic the archiecture of natural extracellular matrix (ECM), a nano-fibrous and micro-porous combined (NFMP) scaffold was fabricated by combining phase separation and particulate leaching techniques. The NFMP scaffold possesses architectural features at two levels, including the micro-scale pores and nano-scale fibers. To evaluate the advantages of micro/nano combination, control scaffolds with only micro-pores or nano-fibers were fabricated. Cell grown in NFMP and control scaffolds were characterized with respect to morphology, proliferation rate, diffentiation and adhesion. The NFMP scaffold combined the advantages of micro- and nano-scale structures. The NFMP scaffold nano-fibers promoted neural differentiation and induced "3-D matrix adhesion", while the NFMP scaffold micro-pores facilitated cell infiltration. This study represents a systematic comparison of cellular activities on micro-only, nano-only and micro/nano combined scaffolds, and demonstrates the unique advantages of the later. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 26: 838-846, 2010