〔Abstract〕 Objective To investigate the clinical effect of intramuscular injection of epinephrine into the anterolateral thigh in the treatment of severe allergic reaction. Methods A total of 60 patients with severe anaphylaxis from grade Ⅱ ~ Ⅳ admitted to Dongguan Chang'an Hospital from January 2018 to July 2022 were divided into two groups with 30 cases in each group according to different administration methods of epinephrine. The observation group for patients with anaphylaxis Ⅱ ~ Ⅳ, use epinephrine solution in the thigh 1/3 anterolateral deep intramuscular injection, for patients with severe anaphylaxis Ⅳ, combined with epinephrine (1:10000) intravenous injection. The control group was given subcutaneous injection of epinephrine stock solution for the patients with grade Ⅱ ~ Ⅳ anaphylaxis, while the patients with grade Ⅳ severe anaphylaxis were given sequential epinephrine intravenous injection (1:10000). The changes of vital signs, circulation stability time and total dosage of epinephrine before and after the intervention were compared between the two groups, as well as the adverse reactions during the intervention. Results After intervention, the heart rate and respiratory rate of the two groups were lower than before intervention, and the mean arterial pressure was higher than before intervention, and the heart rate and respiratory rate of the observation group were lower than those of the control group, and the mean arterial pressure was higher than that of the control group, the differences were statistically significant (P < 0.05). The circulation stabilization time of the observation group was shorter than that of the control group, and the total dosage of epinephrine was less than that of the control group, the differences were statistically significant (P < 0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, the difference was statistically significant (P < 0.05). Conclusion For patients with different levels of severe allergic reactions, the use of anterolateral deep intramuscular injection in the middle 1/3 of the thigh combined with intravenous epinephrine injection (1:10000) showed better therapeutic effects and fewer adverse reactions.