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Background Collagen is a natural constituent of connective tissue and a major structural protein of any organs, with low immunogenicity, biocompatible, non-toxic and fully biodegradable.Capsaicin has the role of anti-scar hyperplasia, but has human skin irritation that produces a burning sensation.Thus, considering the nature characteristics of the collagen and capsaicin;collagen sponge was designed to be the carrier for capsaicin.The aim of study reported here was to evaluate wound healing activity of capsaicin-collagen sponge.Methods Full-thickness defect (2mm×2mm) were created on the back of rats.Capsaicin-Collagen sponge (CCS),Collagen sponge (CS),Rauer Collagen sponge (RCS) and Capsaicin(CAP) were applied topically on open excision wounds, and collection of granulation tissue were done on days 6,12,18,24,30 post wound.The wound healing activity of capsaicin-collagen sponge was evaluated by the wound contraction,collagen synthesis,tensile strength, ELISA assay of TGF-β1 and histopathological.Results In the present study, the wound contraction treated with CCS was significantly higher than the capsaicin-treated group.The CCS-treated rats increased the expressions of transforming growth factor-betal (TGF-β1) on day 30.Histopathologically;more fibroblast proliferation was evident in the CCS-treated group, as compared to the control group and capsaicin-treated group.Immunohistochemistry of CD31 on day 30 revealed significant higher microvessel density in CCS-treated wounds, effectively promote blood vessel ingrowths.Picrosirius staining demonstrated higher collagen fraction in CCS-treated wounds has no significant difference compared to the normal skin.Conclusion In this study, we concluded that capsaicin-collagen sponge play an important role in accelerating the wound healing.