Curcumin has exhibited a protective effect against development of renal fibrosis in animal models, however, its underlying molecular mechanisms are largely unclear. Therefore, we investigated the anti-fibrosis effects of curcumin in transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-β1 or curcumin alone, or TGF-β1 in combination with curcumin. The effect of curcumin on cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of E-cadherin, cytokeratin, vimentin, alpha smooth muscle actin (α-SMA), fibroblast-specific protein 1 (FSP1) and key proteins of Akt/mammalian target of rapamycin (mTOR) pathway were analyzed by immunocytochemistry, real-time PCR and Western blot. Low dose curcumin (3.125 and 25 µmol/L) effectively promoted HKC proliferation. When HKCs were co-incubated with TGF-β1 and curcumin for 72 h, curcumin maintained the epithelial morphology in a dose-dependent manner, decreased expression of vimentin, α-SMA and FSP1 normally induced by TGF-β1, and increased expression of E-cadherin, cytokeratin. Importantly, we found that curcumin reduced Akt, mTOR and P70S6K phosphorylation, effectively suppressing the activity of the Akt/mTOR pathway in HKCs. Curcumin also promoted HKC proliferation, and antagonized TGF-β1-driven EMT through the inhibition of Akt/mTOR pathway activity, which may suggest an alternative therapy for renal fibrosis.