Fingolimod (FTY720) mediated its effects by inhibiting the activation of Mothers against decapentaplegic homologue (Smad)2/3 and phosphatidylinositol 3‐kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K/AKT/GSK3β). Rat renal fibroblast normal rat kidney (NRK)‐49F cells were deprived of serum in the culture medium for 12 h before incubation with FTY720 (5 μM), transforming growth factor (TGF)‐β (2 μg/ml) or TGF‐β plus FTY720 for 12 h. The cells were lysed, and total protein was extracted for Western blot analysis. The phosphorylation levels of Smad2/3 and Smad2 were increased significantly after TGF‐β treatment, and this effect was inhibited by FTY720 (a). The optical densities of P‐Smad2/3 and P‐Smad2 were normalized to that of GAPDH (a). FTY720 also reversed the up‐regulation of phospho‐PI3K signalling, including P‐AKT and P‐GSK3β, but not P‐PI3K (b). The optical densities of P‐PI3K, P‐AKT and P‐GSK3β were normalized to that of GAPDH (b). The data are presented as the mean ± standard error of the mean (s.e.m.). **P < 0·01 relative to the control or FTY720‐treated groups. ***P < 0·001 relative to the control or FTY720‐treated groups. The data represent the results from at least three independent experiments.