Hydrofluoric acid (HFA) is used widely in many industrial processes. There have been many reports on the acute lethal effects of HFA in relation to occupational accidents. This study was designed to investigate the time-dependent harmful effects after exposure of sub-toxic doses. The serum fluoride ion (F) kinetics is also considered in the discussion of the relationship between the concentrations of serum HFA and the disorders. Rats were intravenously injected with HFA (1.6 or 9.6 mg/kg body weight) for the dose-response relationship study. For each dose, the rats were assigned to one of seven groups. Blood samples of the 0-min group were obtained from the carotid artery prior to injection as control. The other six groups were classified according to sampling times (5, 10, 30, 60, 120 and 300-min) for the time-dependent study. The 1.6 mg/kg dose decreased the ionized calcium (Ca2+) level significantly after 30 min, and it also decreased total calcium (Ca) level after 300 min. The 9.6 mg/kg dose rapidly worsened renal dysfunction after 60 min. It increased the serum potassium level after 60 and 120 min and it decreased Ca and Ca2+ levels until 300 min. Although the respiratory compensation functioned, the base excess and HCO3 – level and did not completely recover after 300 min. F concentration rapidly increased in the 5-, 10-, 30- and 60-min group, and it showed no apparent differences in the 120- and 300-min groups compared with the control. Because kidney is a target organ of F, renal dysfunction could be caused by even sub-toxic dose. Although the serum concentration of HFA was diminished, the electrolyte abnormalities and metabolic acidosis would be prolonged, because trace of F could activate K channels and fluorapatite formation for several hours.