We evaluated the acute (up to 24 hours) pathophysiological response to primary blast using a rat model and helium driven shock tube. The shock tube generates animal loadings with controlled pure primary blast parameters over a wide range of field-relevant conditions. The biomechanical loading was evaluated using a set of pressure gauges mounted on the surface of the nose, in the cranial space and in the thoracic cavity of cadaver rats. The mortality rates were established using anesthetized rats exposed to a single blast at five peak overpressures over a wide range of shock intensities (130, 190, 230, 250 and 290 kPa). We observed 0% mortality rates in 130 and 230 kPa groups, and 30%, 24% and 100% mortality rates in 190, 250 and 290 kPa groups, respectively. The intracranial pressure (ICP) oscillations recorded for 190, 250 and 290 kPa groups are characterized by higher frequency (10-20 kHz) than in other two groups (7-8 kHz). The acute bradycardia and moderate lung hemorrhage were noticeable in all groups of rats exposed to the shock wave loading. The onset of both corresponds to 110 kPa peak overpressure, according to the dose-response models. The immunostaining against immunoglobulin G (IgG) of brain sections of rats sacrificed 24-hours post-exposure indicated the diffuse blood-brain barrier breakdown in the brain parenchyma. We observed that the acute response as well as mortality is a non-linear function of peak overpressure and impulse ranges explored in this work.