This thesis work presents a multi-scale mathematical modeling framework to investigate issues regarding vascular smooth muscle contraction. The overall structure of this thesis consists of (1) a model of single vascular smooth muscle cell membrane electrophysiology, contractile system kinetics and cell mechanics; (2) a model of signal transduction of nitric-oxide induced vascular smooth muscle relaxation, and (3) a cellular-based model for myogenic responses of isolated arteries. These models present a general and comprehensive description of VSM contraction and its associated signal transduction, which integrates information from both microscopic (cellular and subcellular interactions) and macroscopic (isolated vessel) levels. These models were utilized to investigate many underlying principles of vascular smooth muscle contraction mediated by multiple signaling pathways and can be applied to study functions of vascular smooth muscle under a variety of physiological and pathological conditions.