Second-harmonic generation (SHG) microscopy provides non-staining observation of collagen structure. Thereby we observed remodeling of collagen gel, in which fibroblasts were embedded or on which endothelial cells (ECs) were cultured. The intensity of SHG light from a fibroblast-embedded gel progressively increased during 7-day culture. In a gel cultured with ECs, SHG intensity markedly increased until day 2, and then the increasing rate of SHG light was decreased. The observation that high SHG intensity area was associated to cell location indicates that the change of SHG intensity was due to interaction between cells and collagen. Because the quantity of collagen produced by cells was insignificant, mechanical interaction is probably major factor.