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The anticancer drug imatinib is an inhibitor of the platelet-derived growth factor receptor (PDGFR) kinases, which are involved in the pathogenesis of fibrotic diseases. In the current study we investigated the delivery of imatinib to the proximal tubular cells of the kidneys and evaluated the potential antifibrotic effects of imatinib in tubulointerstitial fibrosis. Coupling of imatinib to the low molecular weight protein lysozyme via the platinum (II)-based linker ULS yielded a 0.8:1 drug-carrier conjugate that rapidly accumulated in the proximal tubular cells upon intravenous and intraperitoneal administration. The bioavailability of intraperitoneally administered imatinib-ULS-lysozyme was 100%. Renal imatinib levels persisted for up to 3 days after a single injection of imatinib-ULS-lysozyme. Compared with an equal dose imatinib mesylate, imatinib-ULS-lysozyme resulted in a 30- and 15-fold higher renal exposure of imatinib, for intravenous and intraperitoneal administration respectively. Imatinib-ULS-lysozyme could not be detected in the heart, which is the organ at risk for side-effects of prolonged treatment with imatinib. The efficacy of imatinib-ULS-lysozyme in the treatment of tubulointerstitial fibrosis was evaluated in the unilateral ureteral obstruction (UUO) model in mice. Three days UUO resulted in all signs of early fibrosis, i.e. an increased deposition of matrix and production of profibrotic factors. Although a moderately increased activity of PDGFR-β was observed, the profibrotic phenotype could not be inhibited with imatinib mesylate or with imatinib-ULS-lysozyme. Further evaluation of imatinib mesylate and imatinib-ULS-lysozyme is therefore warranted in an animal model of renal disease in which the activation of PDGFR-β is more pronounced.