To explore the therapeutic effect of epinephrine combined with acupuncture on anaphylactic shock and its mechanism. Sixty male Kunming mice were randomly divided into normal saline (NS) group, anaphylactic shock model group, and integrated traditional Chinese and Western medicine treatment group with 20 mice in each group. The anaphylactic shock model was reproduced by egg albumin infusion: intraperitoneal injection of 0.25 mL egg albumin (0.01 mmol/L), repeated injection 1 week later, and intravenous injection of 0.5 mL egg albumin through caudal vein on the 3rd week to induce anaphylactic shock. The mice in the NS group were injected with NS. The mice in the treatment group were immediately subcutaneously injected with 0.2 μg of 0.1% epinephrine, and intraperitoneally injected with aminophylline 0.2 mg, combined with acupuncture at Shuigou, Neiguan and Hegu points. Number of died mice in each group were observed at 1, 6, and 12 hours after model reproduction. The mice were sacrificed at 12 hours, the blood was harvested, and the serum tryptase, immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), interleukins (IL-1 and IL-6) were determined by enzyme linked immunosorbent assay (ELISA). The lung tissues were harvested, and the protein expressions of p65, phosphorylation of p65 (p-p65), and phosphorylation of nuclear factor-κB inhibitor α (p-IκBα) were determined by Western Blot. No mice died in the NS control group at 12 hours. In the treatment group, the mortality at 12 hours was significantly lower than that in the model group (10% vs. 80%, P < 0.01). The levels of tryptase and IgE in the model group were significantly higher than those in the NS control group [tryptase (μg/L): 1.53±0.28 vs. 0.91±0.23, IgE (μg/L): 33.3±3.1 vs. 21.3±1.9, both P < 0.01], both levels in the treatment group were significantly lower than those in the model group [tryptase (μg/L): 1.31±0.26 vs. 1.53±0.28, IgE (μg/L): 25.6±2.2 vs. 33.3±3.1, both P < 0.05]. The levels of TNF-α, IL-1 and IL-6 in the model group were significantly higher than those in the NS control group [TNF-α (ng/L): 35.3±4.7 vs. 16.4±3.5, IL-1 (ng/L): 13.8±3.3 vs. 4.2±1.8, IL-6 (ng/L): 15.3±4.8 vs. 5.5±2.1, all P < 0.01]. The serum inflammatory factors of the treatment group were significantly higher than those of the model group [TNF-α (ng/L): 26.1±4.3 vs. 35.3±4.7, IL-1 (ng/L): 7.2±2.7 vs. 13.8±3.3, IL-6 (ng/L): 8.8±3.8 vs. 15.3±4.8, all P < 0.05]. It was shown by Western Blot results that there was no significant difference in p65 protein expression of the lung tissue among the three groups. In the NS control group, the expression of p-p65 protein in the nucleus of the lung tissue was extremely low but was significantly increased in the model group, and p-p65 protein in the treatment group was significantly decreased as compared with that in the model group. The expression tendency of p-IBα protein was consistent with that of p-p65. Epinephrine combined with acupuncture plays a therapeutic role in mice with anaphylactic shock by inhibiting the activation of NF-κB signaling pathway.