The progress in molecular targeting therapy includes two tides, namely, small molecule compounds and large molecule biological agents. Although the latter prevails in the field of clinical immunology, the former attracts more and more attention in these few years. Most of molecular targeting small compounds are the inhibitors of tyrosine kinases, including pioneering imatinib which inhibits the receptor for platelet-derived growth factor (PDGF), c-Abl, etc. The therapeutic concentrations of imatinib almost completely abrogated the morphological alteration and proliferation of fibroblastic cells induced by PDGF stimulation in 3-dimensional culture system in vitro. Indeed, imatinib has been shown to be effective in various animal disease models for arthritis, interstitial pneumonia, glomerulonephritis, and pulmonary hypertension. Furthermore, its efficacy in patients with systemic sclerosis has been recently reported from several institutes. Since established treatments had not been found for fibrotic lesion before, imatinib, a dual inhibitor of both transforming growth factor beta-, and PDGF-signaling, is likely to be a potent drug against fibrosis. Its efficacy and safety in fibrotic and immune-mediated diseases, such as systemic sclerosis, are currently under investigation throughout the world.