Phenotypic changes can be found in certain glomerular diseases, and the cell origin is not defined. This study was designed to identify whether podocytes can differentiate by the expression of α-smooth muscle actin (α-SMA), under the effects of TGF-β 1 (transforming growth factor-β 1 ) and integrin. Western and Northern blot analyses were performed to identify the protein and mRNA (messenger ribonucleic acid) expression of α-SMA. The number of podocytes, which express α-SMA, was measured by immunocytochemical staining. The results showed that TGF-β 1 dose-dependently increased α-SMA protein and mRNA expression at 4 and 2 days, respectively. TGF-β 1 also dose-dependently increased the α-SMA staining of podocytes. The α-SMA-positive podocytes showed front-end and back-end polarity. The integrinα3β 1 antagonists, anti-integrinβ 1 monoclonal antibody and Gly-Arg-Gly-Asp (GRGD), decreased the expression of α-SMA protein and the percentage of α-SMA positive cells stimulated by TGF-β 1 (both P < 0.01). The addition of calphostin [inhibitor of protein kinase C (PKC)] and genistein [inhibitor of focal adhesion kinase (FAK)] also decreased the expression of α-SMA protein and the percentage of α-SMA positive cells stimulated by TGF-β 1 (both P < 0.01). In conclusion, this study indicated that TGF-β 1 may act synergistically with integrins, through activation of PKC and FAK, to induce the phenotypic changes of rat podocytes with increasing α-SMA expression.