Purified carbon nanotubes (with removed toxic catalytic particles) have been considered as novel materials for drug delivery and for generating artificial organs more efficiently than traditional tissue engineering materials due to their unique surface features. The surface chemistry of carbon nanotubes has been modified through various functionalization strategies to increase biocompatibility. Importantly, modulating the intrinsic material surface energy of carbon nanotubes (without functionalization, thus, establishing permanent, non degradable chemical, and physical surface properties) can potentially reduce an immune response mediated by macrophages. Herein, we report macrophage responses on different surface energy carbon nanotubes while keeping their nanoscale surface roughness. Specifically, interactions of ultra hydrophobic (bare or unmodified) and hydrophilic carbon nanotubes (due to the formation of oxide layers) with macrophages were investigated. It was observed that macrophage density on both carbon nanotube scaffolds were lower than on traditional materials. In particular, the amount of released cytokine (TNF-α) from macrophages cultured on hydrophilic carbon nanotube scaffolds was much smaller than on hydrophobic carbon nanotube scaffolds. All results clearly supported that tailoring the surface energy of carbon nanotubes mediates a macrophage immune response.