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Objective: To investigate the effect of substance P (SP) on gene expression of transforming growth factor β-1 (TGFβ-1), transforming growth factor receptor-1 (TGFR-1) and transforming growth factor receptor-2 (TGFR-2) in fibroblasts cultured in vitro from rats granulation tissues.Methods: The fibroblasts from the granulation tissues in the skeletal muscle of rats hind limbs injured by formaldehyde were cultured in vitro. When different concentrations (10-9-10-5 mol/L) of SP were added into the culture medium, the changes of gene expression of TGFβ-1, TGFR-1 and TGFR-2 in the cultured fibroblasts were observed with reverse transcription polymerase chain reaction at different intervals (0, 3, 6, 12 and 24 hours after incubation).Results: The gene expression of TGFβ-1, TGFR-1 and TGFR-2 in the fibroblasts cultured from rats granulation tissues was up-regulated by SP. The peak level of the mRNA expression was found at 10-8 mol/L SP and the up-regulation effect was not found at 10-5 mol/L and 10-6 mol/L. The peak levels of gene expression of TGFβ-1, TGFR-1 and TGFR-2 in the fibroblasts treated with SP were achieved at 6 and 12 hours, respectively.Conclusions: SP has up-regulation effect on the gene expression of TGFβ-1, TGFR-1 and TGFR-2 in fibroblasts from rats granulation tissues in vitro, and the effect is related to different stimulating concentrations of SP. It may be concerned with proliferation and differentiation of fibroblasts and formation of scar tissues during wound healing.