Transforming growth factor-β (TGF-β) induces Epithelial-mesenchymal transition (EMT) through varying cell-cell communications, including autocrine, paracinre and endocrine signalling. Recent studies discovered that exosomes are important carriers of signalling molecules, including TGF-β in intercellular communications. However, whether and how exosomal TGF-β may differ from the free ligand TGF-β in intercellular communication is unclear. We investigated free ligand and exosomal TGF-β signalling in three TGF-β signalling component-defective cell lines, including R1B (TGF-β type I receptor-defective), DR26 (TGF-β type II receptor-defective) and T84 (Smad4-defective) cells. The free ligand TGF-β failed to activate TGF-β signalling in these cells. Surprisingly, TGF-β active exosomes derived from MDA-MB-231 cells restored TGF-β signalling in R1B and DR26 cells but not in T84 cells, suggesting it is possible that TβRI and TβRII, but not Smad4, are carried in the TGF-β active exosomes. To confirm the presence of TβRI and TβRII in exosomes, we overexpressed either TβRI or TβRII in HEK293T cells. Western Blot analysis demonstrated the presence of and TβRI and TβRII in exosomes derived from transfected cells. Furthermore, when co-cultured with fibroblasts NIH3T3 cells, R1B and DR26 cells restored TGF-β signalling activity, and the signalling was further enhanced upon free-ligand TGF-β treatment. It is possible that during cell-cell communication, NIH3T3 fibroblasts secrete TGF-β receptors-containing exosomes and restore TGF-β signalling in receptor-defective cells. In conclusion, we discovered the functional difference between free ligand and exosomal TGF-β. While free ligand TGF-β requires TGF-β receptors to transduce signalling, exosomal TGF-β, on the other hand, has the capacity to transduce receptor-independent signalling in recipient cells.