This work reported the wetting and spreading behavior of pure iron droplet on single crystal TiO2 substrate. During the heating process, a "FeO center dot TiOx separated liquid phase" appeared at the temperature below the melting point of the pure iron, and completely covered the lower half of the iron droplet. The observed high-wetting behavior of the droplet is due to the spreading of the "separated liquid phase" rather than the iron droplet flow. According to both thermodynamic considerations and experimental measurements, the "separated liquid phase" is formed through the chemical interactions among the iron specimen, oxygen gas in the Ar atmosphere and TiO2 substrate.