Current understanding on the interactions between micro/nano-structured Ti surfaces and macrophages is still limited. In this work, TiO2 nano-structures were introduced onto acid-etched Ti surfaces by alkali-heat treatment, ion exchange and subsequent heat treatment. By adjusting the concentration of NaOH during alkali-heat treatment, nano-flakes, nano-flakes mixed with nano-wires or nano-wires could formed on acid-etched Ti surfaces. The micro- and micro/nano-structured Ti surfaces possessed similar surface chemical and phase compositions. In vitro results indicate that the morphology of macrophages was highly dependent on the morphological features of nano-structures. Nano-flakes and nano-wires were favorable to induce the formation of lamellipodia and filopodia, respectively. Compared to micro-structured Ti surface, micro/nano-structured Ti surfaces polarized macrophages to their M2 phenotype and enhanced the gene expressions of osteogenic growth factors in macrophages. The M2 polarized macrophages promoted the maturation of osteoblasts. Compared to that with nano-flakes or nano-wires, the surface with mixed features of nano-flakes and nano-wires exhibited stronger anti-inflammatory and osteo-immunomodulatory effects. The findings presented in the current work suggest that introducing micro/nano-topographies onto Ti-based implant surfaces is a promising strategy to modulate the inflammatory response and mediate osteogenesis.