In this paper，two kinds of synthetic cores with a wettability index（WI）in the range of?0.7-0.7 are comparatively used to explore the main difference in the influence of wettability on waterflooding characteristics of ultra-low permeability and medium-high permeability cores. The results reveal that for the homogeneous cores with ultra-low and medium-high permeability，the influence trend of wettability on waterflooding characteristics is similar. Specifically，stronger lipophilicity and hydrophilicity of cores（more deviated from the medium wettability）are accompanied by the faster breakthrough of waterflooding front，a higher rising rate of average water cut，a higher waterflooding equilibrium pressure gradient，and lower water-free oil displacement efficiency and ultimate oil displacement efficiency. The difference is reflected in the magnitude of the influence of the characteristic parameter values. Compared with the medium-high permeability cores，the ultra-low permeability cores are much more susceptible to the influence of the wettability index on aspects including the rising rate of average water cut，equilibrium pressure gradient，and ultimate oil displacement efficiency. The waterflooding characteristics of ultra-low permeability reservoirs are more sensitive to wettability compared with those of medium-high permeability reservoirs. The transition of wettability from oil-wet to medium-wet in ultra-low permeability reservoirs has much greater technical potential for improving oil displacement efficiency than that in medium-high permeability reservoirs.