Purpose : Infusion therapy has recently been applied for slight dip-related scarring or facial wrinkles. Clinical knowledge about infusion therapy has increased, but few reports have described tissue reactions following injection and the disintegration/absorption process. We compared tissue reactions after injection between hyaluronic acid and a collagen drug used as infusion 'Filler' in this study. Subject and Methods : Using 3 types of filler (Restylane and Restylane Perlane as non-animal stabilization hyaluronic acid and Zyplast as cross-linked bovine dermal collagen), Japanese white rabbits were subcutaneously injected in the auricular concha and histological and immunological investigations were performed. Results : Acute inflammation with infiltration of numerous eosinophils was seen following hyaluronic acid injection in the early stages, but inflammation disappeared by day 14 after injection and hyaluronic acid was present in the tissue thereafter. An englobement absorption image by foreign body giant cells of hyaluronic acid was more marked 60 days after application and most were absorbed by 180 days. Conversely, in the group with collagen injection, cell infiltration was seen during the early stage, and continued thereafter, with histological examination revealing migration/increased fibroblasts and angiogenesis. Granulation tissue formation with marked infiltratation of inflammatory cells was seen up to 150 days, suggesting strong tissue reaction during observation. Conclusions : Ideal filler satisfies the conditions of safety, efficacy, biocompatibility, non-immunogenicity, long-term stability, low cost and absorbency. As for hyaluronic acid filler, tissue reaction was relatively weak, making this approach comparatively ideal compared to collagen-type filler.