This paper presents the synthesis of highly biocompatible and biodegradable poly­(lactide-co-glycolide) (PLGA) microchamber arrays sensitive to low-intensity therapeutic ultrasound (1 MHz, 1–2 W, 1 min). A reliable method was elaborated that allowed the microchambers to be uniformly filled with epinephrine hydrochloride (EH), with the possibility of varying the cargo amount. The maximum load of EH was 4.5 μg per array of 5 mm × 5 mm (about 24 pg of EH per single microchamber). A gradual, spontaneous drug release was observed to start on the first day, which is especially important in the treatment of acute patients. Ultrasound triggered a sudden substantial release of EH from the films. In vivo real-time studies using a laser speckle contrast imaging system demonstrated changes in the hemodynamic parameters as a consequence of EH release under ultrasound exposure. We recorded a decrease in blood flow as a vascular response to EH release from a PLGA microchamber array implanted subcutaneously in a mouse. This response was immediate and delayed (1 and 2 days after the implantation of the array). The PLGA microchamber array is a new, promising drug depot implantable system that is sensitive to external stimuli.