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Cellulose derivatives have got growing interest due to their relative abundance and ability to sustain the release of medicaments. In this study, micro- and nano-fibrillated cellulose were prepared from rice straw and used as drug carriers. Both carriers in addition to another one which is nano silicon dioxide were characterized with various techniques. Methotrexate was chosen to be loaded on nano-fibrillated cellulose and nano silicon dioxide. Both methotrexate carriers were evaluated for their possible protective role against renal fibrosis induced by methotrexate in leukemia rat model. Results of this study exhibited that loading methotrexate on either nano-fibrillated cellulose or nano silicon dioxide seems to have an ameliorative role on renal function tests, inflammatory and fibrotic markers of renal tissues. Moreover, the sustained release of methotrexate for long time period maintained by nano-fibrillated cellulose carrier gives it more priority than nano silicon dioxide to be used as an effective novel drug carrier in further medical applications with minimal side effects on kidney tissue in leukemia model., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest concerning this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)