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Introduction: Considered as an end-stage for all cardiovascular diseases, cardiac fibrosis leads to the development of heart failure, thus the ultimate goal is to prevent the progression of fibrosis. Indeed, heart can regenerate itself but to a certain limit based upon the number of resident stem cells which is limited. Thus, stem cells transplantation is considered as a promising therapy. This study aims to examine if MSC transplantation can inhibit the progression of myocardial fibrosis in rat model compared to Colchicine treatment; and if the timing of treatment with MSCs or COL affect the progression of fibrosis. Material & Methods: To induce cardiac fibrosis in 48 female albino rats, Isoproterenol hydrochloride was used. These rats were divided into 2 models: COL-treated group that were treated after 1,2,3 weeks of the last ISO injection by colchicine orally. MSC-treated group that were injected intravenously after 1,2,3 weeks of last ISO injection by MSC. Heart rate and Systolic blood pressure were measured and the levels of Creatine phosphokinase, Lactate dehydrogenase, Matrix Metalloproteinase II and Collagen I were assessed. Moreover, cardiac tissues were examined hitopathologically. Results & Conclusion: MSC were proved to enhance the effect of anti-remodeling of extracellular matrix significantly by modulating the expression of matrix metalloproteinases, which is superior to COL treatment.