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Abstract Arginase, a binuclear manganese metalloenzyme in the urea, catalyzes the hydrolysis of L-arginine to urea and L-ornithine. Both isoforms, arginase 1 and arginase 2 perform significant roles in the regulation of cellular functions in cardiovascular system, such as senescence, apoptosis, proliferation, inflammation, and autophagy, via a variety of mechanisms, including regulating L-arginine metabolism and activating multiple signal pathways. Furthermore, abnormal arginase activity contributes to the initiation and progression of a variety of CVDs. Therefore, targeting arginase may be a novel and promising approach for CVDs treatment. In this review, we give a comprehensive overview of the physiological and biological roles of arginase in a variety of CVDs, revealing the underlying mechanisms of arginase mediating vascular and cardiac function, as well as shedding light on the novel and promising therapeutic approaches for CVDs therapy in individuals.