The purpose of this study was to reveal the mechanism of acute lethal accident after the exposure of human on face to a diluted solution of hydrofluoric acid (HFA). Particles of HFA solution and saline (50 µL) were intratracheally (i.t.) sprayed to rats using an aerosol generator as examples of inhalation exposure to HFA and control, respectively. A lethal dose (LD) study showed that the 24 h LD50 i.t. and LD99i.t. were 0.58 and 1.92 mg/kg, respectively ; 1.92 mg/kg can cause mortality within several hours after the exposure to satisfy the model of the accident. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were sampled 1 h after the i.t. administration of HFA (1.92 mg/kg) and saline for the biological exposure and effect monitoring. Blood parameters indicated severe respiratory acidosis without apparent abnormalities of serum electrolytes. Semiquantitative grading of pathohistological findings revealed that there were mild hemorrhage and effusion in alveolar spaces in the HFA group. The level of surfactant protein D in the BALF of the HFA group was much lower than that of the control. It was considered that the respiratory failure would be mainly due to the deficiency of the surface acting agent in the alveolus caused by the retained HFA in the alveolar spaces. Hyperpotacemia and hypocalcemia were the main causes of mortalities in many clinical cases after HFA exposure. However, it was confirmed that the strong mortality after the inhalation of HFA aerosols could be derived from the pulmonary dysfunction without abnormalities of serum electrolytes in this study.