Accidental injection of local anesthetics containing epinephrine into a digit can cause distal tissue necrosis. Norepinephrine infiltration in subcutaneous tissue also causes tissue necrosis. Phentolamine has been used to prevent necrosis from norepinephrine. Because both epinephrine and norepinephrine are alpha- and beta-adrenergic stimulators, the rat foot model was developed to study the possible use of phentolamine or labetalol in protection against tissue necrosis after injection of epinephrine in the extremity.Phentolamine was found to be useful in preventing tissue necrosis after the injection of local anesthetic containing epinephrine in the skin of the rat foot. Labetalol was found to be less effective in preventing tissue necrosis. Phentolamine may be useful in preventing tissue necrosis after the inadvertent injection of epinephrine containing local anesthetics in the digit.