Objective To investigate the effect and mechanism of melatonin on bioactivity of fibroblasts from human hypertrophic scar.Methods Fibroblasts from hypertrophic scar were cultured and incubated with melatonin,melatonin and Luzindole,and Luzindole,respectively,for 24 h,and the media as control.XTT/PMS assay was used to measure the proliferation of fibroblasts,ELISA assay to detect the TGF-β1 production of fibroblasts,and the expression of cell a-SMA,collagen Ⅰ,collagen Ⅲ mRNA were determined with real-time PCR method.Results Compared with the control,melatonin at the concentration of 10-5mmol/L,10-3mmol/L,and 1 mmol/L could inhibit the proliferation of fibroblasts in a does-dependent manner (P＜0.05); melatonin at the concentration of 10-3 mmol/L could significantly decrease the TGF-β1 production and expression of a-SMA mRNA and collagen Ⅰ mRNA in fibroblasts from human hypertrophic scar (P＜0.05) ; the effect of melatonin on fibroblast was significantly blocked by Luzindole (P＜0.05),but melatonin could not inhibit collagen Ⅲ mRNA expression (P＞0.05).Conclusions Melatonin can significantly regulate the biological activity of fibroblasts from human hypertrophic scar through a receptor pathway.