There are several in vitro cell models for studying the interactions of carbon nanotubes (CNTs) with biological systems. This chapter provides a detailed protocol for studying the effects of CNTs on cell adhesion and spreading. The protocol is a combination of methods of electron microscopy, cell biology, and molecular biology, focusing on the detection of the cell morphology and cellular responses related to cell adhesion and spreading process, including the observation of cellular skeletal changes upon cell adhesion, the measurement of the expression level changes of cell adhesion, and the spreading specific genes and proteins upon exposure to CNTs.