Prolonged stress on blood vessels induces chronic inflammation, as well as the dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs), leading to vascular remodeling. Pressure overload, one of the major stresses causing vascular remodeling, depolarizes VSMCs and results in Ca²⁺ influx through voltage-dependent Ca²⁺ channels (VDCCs). We have hypothesized that sustained depolarization induces excitation-transcription coupling (E-T coupling) in VSMCs and upregulates proinflammatory genes mainly using ex vivo preparations. To examine if sustained depolarization of VSMCs induced the E-T coupling and vascular remodeling in live mice, we utilized an optogenetic approach using mice expressing ChR2 specifically in smooth muscle (SMC-ChR2-YFP). We confirmed VSMC-specific expression of ChR2 in the carotid arteries of SMC-ChR2-YFP mice. Light stimulation successfully induced an increase in cytosolic [Ca²⁺] through VDCCs in VSMCs freshly isolated from mouse carotid arteries. Similar results were obtained in tissue preparations from carotid arteries. Furthermore, light stimulation of the carotid arteries in vivo induced pro-inflammatory gene transcription. These results suggest that sustained depolarization specific to VSMCs can cause E-T coupling in vivo and trigger vascular inflammation, which potentially lead to vascular remodeling.