Abstract: Objective To study the influence of quedcetin on the collagen synthesis of cultured fibroblast, and to explore the mechanism of the effect. Methods The inhibitory effects of quercetin and radiation on fibroblast proliferation were assayed using MTT assay. Collagen synthesis was detected by hydroxyproline colorimetric analysis. Immunocytochemical staining method was used to investigate the expression of collagen I and III of fibroblasts. The mRNA expression of type I, type III collagens and TGFβ-1 were assayed by using reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR technique. Results Keloid fibroblast cell proliferation and collagen synthesis of fibroblasts could be inhibited by quercetin in a dose-dependent manner. Significant inhibition was observed by the treatment with quercetin and radiation together. Immunocytochemical staining indicated the IOD of type I and III collagen protein was down-regulated by quercetin and radiation. Both collagen I and collagen III gene in the quercetin groups showed a significantly decreased mRNA expression compared with that in the untreated group，especially in the group treated with both quercetin and X-ray. Procollagen gene expression could be inhibited to prohibit type I and III protein syntheses of fibroblsts by inhibiting gene transcription (p<0.05), particularly type I procollagen gene (p<0.01). The mRNA level of TGFβ-1 gene could also be down-regulated by quecertin, which was probably the mechanism of the drug effect. Conclusions Quercetin associated with radiation can considerably inhibit collagen synthesis of keloid-derived fibroblast by decreasing the mRNA expression in vitro. The result is mainly accomplished by the down-regulated effect on TGF β-1 gene level.