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The search for safe and effective tissue fillers has been an ongoing effort in plastic and cosmetic surgery over recent decades. Biocompatibility is a prerequisite for any substance to be used as an implant material, and potential biomaterials need to be characterized by histologic evaluation of tissue responses. Collagen is a well-known tissue filler. Agarose gel is widely used in bioengineering. Both products are considered biocompatible. The purpose of this study was to evaluate the bioactivity of agarose gel as a dermal filler compared with collagen.Tissue responses to agarose gel and collagen were evaluated in a rat in vivo model (n = 96). Four groups were evaluated: group 1 (n = 24), rats with agarose gel implants; group 2 (n = 24), rats with collagen implants; group 3, a placebo group (n = 24); and group 4, a control group (n = 24). Responses and biocompatibility were assessed by histopathologic and histomorphometric evaluation at 1 week to 8 months after implantation.Agarose gel showed marked bioactivity and biodegradation, although the implants integrated well into tissues: newly formed collagen bands were observed inside the implants and no granulomas were detected. Collagen implants showed low cell infiltration and a significant loss of product over time.Agarose gel is a biocompatible product that can be considered for use as a tissue filler. Further investigation is required to assess its long-term efficacy and safety.