The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of diabetic vascular complications. In high-glucose (HG) conditions, endothelial cells (ECs) act as the first barrier to damaging stimuli and trigger a multi-response, including EC and VSMC crosstalk. However, the crosstalk pathways between ECs and VSMCs under HG conditions remain unclear. This study aimed to explore the roles and underlying mechanism of exosomes derived from ECs in the crosstalk between ECs and VSMCs. Our results showed that mouse aortic endothelial cell (MAEC)–secreted exosomes could promote the proliferation and inhibit the apoptosis of VSMCs induced by HG. Furthermore, we isolated the exosomes secreted by MAECs and found that exosomes derived from MAECs that were exposed to HG could transfer circHIPK3, which is enriched in MAEC-derived exosomes, to VSMCs. Exosomal circHIPK3 promoted the proliferation and inhibited the apoptosis of VSMCs. circHIPK3 sponged miR-106a-5p to relieve its repression of forkhead box O1 (Foxo1) expression. The increased expression of Foxo1 acted as a transcription factor to promote Vcam1 expression, thus facilitating the uptake of MAEC-derived exosomes by VSMCs. The results of this study suggested that exosomal circHIPK3 derived from MAECs promotes the proliferation of VSMCs induced by HG via the miR-106a-5p/Foxo1/Vcam1 pathway.