Mesenchymal stem cells (MSCs) can differentiate into neurons, which can be used in cell therapy. Endogenous genes and neurotrophic factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 regulate neural stem cell proliferation and differentiation (NT-3). The differentiation of MSCs into neurons is characterized by the development of neurons that interact with each other to form rings or net-like structures. The markers of neurons in the immature stage are Nestin and Vimentin. While the markers for neurons at the mature stage are neuron-specific enolase (NSE), neuronalspecific nuclear protein (NeuN), and microtubule-associated protein-2 (MAP-2). This research aims to investigate the expression of MAP-2 on the differentiation of MSCs into mature neurons. MSCs were isolated from rat bone marrow of femur and tibia using flushing methods, then cultured in Minimum Essential Medium Eagle (MEM), 10% Fetal Bovine Serum (FBS), and 1% antibiotic-antimycotic. Neuron differentiation induction medium (MEM, 2% FBS, 1% insulin-like growth factor (N2), and NT-3 20, 25, and 30 ng/mL) was used to stimulate MSCs for 14 days (control induction medium without NT-3). The immunocytochemistry of MAP-2 was performed on day 14. All experiments were done triplicated. The data obtained is the average percentage of the number of MAP-2 positive cells at each concentration. SPSS statistical analysis with a one-way ANOVA test. The results showed a significant difference between the percentage of MAP-2 positive cells at NT-3 concentrations 20 (p < 0.05), 25 (p = 0,093), 30 ng/mL (p = 0,081), and the negative control. At concentrations of NT-3 20, 25, and 30 ng/mL the