BACKGROUND Bone marrow stromal cells (BMSCs) have an important application prospect in the field of cell therapy for various neurodegenerative diseases, and inducing factors that regulate BMSC differentiation are proposed as a promising therapeutic strategy. In this study, we explored the effect of glial cell-derived neurotrophic factor (GDNF) on the course of BMSC differentiation. METHODS BMSCs were isolated from rat bone marrow and induced by GDNF. The effects of GDNF on BMSC viability and proliferation were verified by cell counting kit-8, MTT, bromodeoxyuridine, and flow cytometry assays. Neuronal differentiation from BMSCs was detected by quantitative real-time polymerase chain reaction and immunofluorescence via measuring the expression of several neural specific markers. RESULTS Compared to untreated BMSCs, GDNF induced the differentiation of BMSCs into neuron-like cells and enhanced the expression levels of neuronal markers including nestin and NCAM. Moreover, the expression of SCF was suppressed by GDNF stimulation. CONCLUSIONS GDNF could elevate the differentiation of BMSCs into neuron-like cells and could be considered as an effective candidate cell for future neuroscience research.