Aim To study the function of microRNA-124-2 in the process of which CD137-CD137L interaction regulates the NFATc1 in mouse vascular smooth muscle cells. Methods With the stimulation/inhibition of CD137-CD137L axis by anti-CD137/anti-CD137L, RT-PCR technique was used to detect the expression of microRNA-124-2 in mouse vessel smooth muscle cells(VSMC). Liposomal transfection was used to transfect microRNA-124-2 mimic and inhibitor into mouse VSMC, then the change of NFATc1 mRNA and protein expressions was analyzed by qRT-PCR and Western blot after stimulated with anti-CD137/anti-CD137L in the corresponding group. Luciferase Reporter Assay system was used to validate the role of microRNA-124-2 for NFATc1-3′UTR. Results Compared with the control group,the expression of microRNA-124-2 had reduced after stimulated by anti-CD137(0.29±0.13 vs 1.00±0.00, P<0.05), and increased by anti-CD137L(3.42±0.17 vs 1.00±0.00, P<0.05). The regulation of CD137-CD137L axis to NFATc1 could be reversed by transfected with mimic or inhibitor. Dual-Luciferase activity assay showed that microRNA-124-2 had an inhibition on NFATc1-3′UTR(0.283±0.011 vs 1.294±0.143,P<0.001). Conclusions microRNA-124-2 could be regulated by CD137-CD137L interaction and thus affect NFATc1’s expression.