Chronic lesion has become a major biological burden for individual patients and health organizations. Using nanoparticles as drug delivery systems is remarkable nowadays. The unique properties of chitosan without any toxicity for living creations make it a suitable option for drug delivery. Epidermal growth factor (EGF) is one of the important agents for wound healing, cellular proliferation, extracellular matrix formation, and skin remodeling. A combination of these properties can accelerate the wound healing process. In this study, rh-EGF is embedded into the chitosan nanoparticles by the Ion-gelation method. Nanoparticles are characterized by TEM microscopy and the DLS method and conjugation efficacy is measured by FT-IR radiation. The antibacterial effect of manipulated nanoparticles was estimated by MIC/MBC methods. The cytotoxicity and proliferation were measured by MTT assay on the HFF-1 human fibroblast cell line. Migration assay was accomplished by in vitro scratch model and the gene expression analysis for TGF-β, VEGF, and PDGF were manipulated by the real time-PCR method. The obtained results were considered statistically significant with P < 0.05. Obtained results illustrated no toxic effect on the HFF-1 cell line treated with Chitosan-EGF (CS-EGF). In cellular proliferation and migration assays, CS-EGF nanoparticles demonstrated a better effect than free rh-EGF. For the duration of 72h of the experiment, the whole scratch was covered by fibroblasts. The real time-PCR analysis also showed upregulation of all TGF-β, VEGF, and PDGF genes. As CS-EGF nanoparticles in the acceleration of the skin remodeling process showed promising results, subsequent studies might be useful.