Objective: Mesenchymal stem cells are present in many human tissues and serve as a readily available source of undifferentiated cells being capable to form specific tissues like bone, cartilage, fat, muscle and tendon. MSCs can be isolated from various adult mesenchymal tissues including synovium. the aim of this study is search the ability of synovium- derived mesenchymal stem cells to differentation to acquire neuronal or glial in vitro. Materials and Methods: MSCs were isolated and cultured from femoral knee joint of baker cyst and ACL(Anterior cruciate ligament)patient and identified with morphological observations and differentiation tests.Then, SMSCs isolated and induced in vitro by β-mercaptoethanol (BME) and retinoic acid (RA). Alizarin red oil red O staining and RT-PCR were done to investigate stemness property of cells. After differentiation, the expression of neuronal markers NF-L (neurofilament- light, or neurofilament 70 kDa) and early neuronal marker NeuroD1 were determined with RT-PCR. Results: Morphological observations, differentiation results and RT-PCR tests revealed that our isolated cells were MSCs. RT-PCR analysis indicated that the RA and BME treated SM- MSCS expressed mRNA transcripts for neuron-specific markers neurofilament proteins (NF-L) and Neurogenic differentiation 1(NeuroD1). Conclusion: These results indicate that human synovial membrane -derived MSCs could trans-differentiate into neural cell types by RA and BME treatment. So in spite of these results, better understanding of SM-MSCs behavior in vitro and in vivo is needed to develop strategies for therapeutic applications by these cells.