Aim To investigate the role of exosomes in the calcification of mouse vascular smooth muscle cells (VSMCs) induced by CD137 signal. Methods The mouse thoracic aorta VSMCs were performed by patch-attaching method, and VSMCs were divided into two groups:the control group, the CD137 excitation group. The exosomes were extracted by kit and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Fluorescence microscopy was used to observe VSMCs uptake of exosomes. Lentiviral vector of nuclear factor of active T cell c1 (sh-NFATc1) was constructed and infected with VSMCs. The experiments were divided into three groups:control group with exosomes treatment, CD137 excitation group with exosomes treatment, silenced NFATc1＋CD137 excitation group with exosomes treatment. Western blot was used to detect the expressions of α-smooth muscle actin (α-SMA), bone morphogenic protein 2 (BMP-2) and Runt-related transcription factor 2 (Runx-2). Calcium salt deposition in VSMCs was detected by Von Kossa staining. Results Western blot results showed that microvesicles in both groups expressed exosomes surface marker proteins CD9 and CD81. Under electron microscopy, the exosomes were round and cup-shaped, and its diameter was about 30-100 nm. The expression of NFATc1 protein increased significantly in exosomes of CD137 excitation group. Compared with the control group exosomes treatment group, the expressions of calcification-related indicators BMP-2 and Runx-2 proteins increased significantly in CD137 excitation group with exosomes treatment, while the expression of α-SMA decreased significantly. Compared with CD137 excitation group with exosomes treatment, the expressions of BMP-2 and Runx-2 proteins decreased significantly in silenced NFATc1＋CD137 excitation group with exosomes treatment, while the expression of α-SMA increased significantly. Von Kossa staining showed that VSMCs calcium deposits in CD137 excitation group with exosomes treatment were more than those in control group with exosomes treatment, while those in silenced NFATc1＋CD137 excitation group with exosomes treatment were significantly lower than those in CD137 excitation group with exosomes treatment. Conclusion CD137 signal pathway mediates VSMCs calcification through exosome transmitting NFATc1.