Objective:To investigate the effect of interleukin-17 (IL-17) on rat renal fibroblast NRK-49F transforming into myofibroblast and expressing extracellular matrix (ECM) as well as the signal mechanism involved. Methods: Western blot detected the effect of IL-17 on NRK-49F cells which was induced by transforming growth factor-β (TGF-β) transforming into myofibroblasts and expressing alpha-smooth muscle actin (α-SMA) and I-collagen and fibronectin. The mRNA expression levels of ECM I-collagen and fibronectin as well as regulatory effect of IL-17 in NRK-49F cells were detected by real-time PCR after 24, 48 and 72 h, respectively. Western blot was performed to detect classical Smad-dependent and Smad-independent signaling of TGF-β and its phosphorylation level, in order to explain molecular mechanism of IL-17 on regulating NRK-49F. Results: IL-17 inhibited NRK-49F cell line transforming into myfibroblast and expressing α-SMA, I-collagen and fibronectin. IL-17 had no effects on the expression of classic Smad signaling molecule, however, it inhibited the activation of Akt-TSC2-p70S6K through Smad-independent signaling pathway. Conclusion: IL-17 inhibits NRK-49F cell line transforming into myfibroblast and expressing α-SMA, I-collagen,and fibronectin by blocking the activation of Akt-TSC2-p70S6K through Smad-independent signaling pathway.