Background & Aims: One of cell- based technical issues associated with cartilage repair assay is delivering cells to the site of the parts where damage is created. Mesenchymal stem cells (MSCs) with their chondrogenic potential are ideal candidates for cartilage regeneration. High expression of cartilage hypertrophy markers by MSCs would result in apoptosis and ossification. This investigation is attempted to find out if paracrine factors secreted from MSCs can regenerate damaged articular in a rat model. Materials & Methods: Osteoarthritis (OA) was induced in eighteen adult rats by intra- articular (IA) injection of monosodium iodoacetate (MIA) into right knee. Then the animals were randomly divided into three groups (n=6). Control group received IA injection of vehicle; MSCs group received a single IA injection of MSCs (2.5×105/50µL DMEM) and conditioned medium(CM) group received a single IA injection of CM, meanwhile six left intact knee joints were taken as the normal group. After four weeks, the animals were scarified by overdose injection of ketamine and then, the distal end of femur removed and fixed in formalin. After decalcification using formic acid, histological slides obtained. In this study number of chondrocytes and morphology of articular surface were evaluated. Results: Four weeks after treatment, gross and microscopic evidence of articular cartilage of distal end of femur cartilage demonstrated the significant (p<0.05) healing of OA joints in group treated with MSCs. Also, in CM group significant increase in number of chondrocyte (p<0.05) and decrease of degenerated holes width was observed compared to the control group. Conclusion: Given the deficiencies of cell-therapy in OA, a potential for repair of degenerated articular cartilage is thought possible to be represented by cell free CM.