Background: Osteoarthritis (OA) is a degenerative disease, which is characterized pathologically by degeneration of articular cartilage. One of the mechanisms of cartilage lesion in OA is decreased synthesis of cartilage matrix and amongst the variety of treatment methods for OA, cell base therapies has a crucial role. Objectives: The purpose of this study was to understand the regeneration effect of mesenchymal stem cells as well as secretions of these cells after induction of early-stage Osteoarthritis (OA). Materials and Methods: To achieve this aim articular cartilages of rat knees were cured by monosodium iodoacetate (1 mg/50 µL). Mesenchymal Stem Cells (MSCs) were cultured and injected into the knee joint of rats after two weeks. The left knee was kept as the control group and injected with either sterill saline. The animals were sacrificed at two weeks after transplantation. The knee joints were harvested and safranin-o and toluidine-blue microscopic analysis were performed. In order to assess changes, the amount of control and experimental cartilage extracellular matrix structure (proteoglycan) and cartilage fibrillation were determined by using histological approaches. Results:The results revealed a decrease of proteoglycan content in the superficial and intermediate zones and presence of surface fibrillation. Therefore, OA induced matrix degeneration, and the reparative effects of MSCs were higher than cell secretions. Conclusions: It can be concluded that due to some bioactive and nutrient factors, MSCs secretions could be used for recovery of OA as well as prevention of articular cartilage matrix degeneration, using a high dose of cell secretions.