Objective To explore the clinical effects and potential regulatory mechanism of combined acupuncture and medicine in the treatment of postviral olfactory dysfunction.Methods 104 PVOD patients were randomly divided into the Control group and the acupuncture-medicine combined group, with 52 patients in each group. Among them, the Control group was given conventional nasal hormone mometasone furoate nasal apray for treatment, and the acupuncture-medicine combined group was given intranasal acupuncture at bilateral Neiyingxiang and Biqiu points on the basis of conventional treatment. Sniffin Sticks test, T & T smell test, and paranasal sinus CT scan were performed before treatment and one month after treatment, also the venous blood of each group was collected. Western blotting was applied to detect the expressions of MyD88, TLR4, and NF-κB p65, and the flow cytometry was used to measure the percentages of CD4⁺CD25⁺ T cells and CD4⁺CD25 ^high T cells.Results Compared with the control group, the difference of TDI score and T & T smell test score, cure rate, improvement rate, CD4⁺CD25⁺ T cells, and CD4⁺CD25 ^high T cells percentages in the acupuncture-medicine combined group were increased (P < 0.05). However, the T & T smell test score, MyD88, TLR4, and NF-κB p65 expressions were decreased (P < 0.05); compared with the indexes before treatment, CD4⁺CD25⁺ T cells and CD4⁺CD25 ^high T cells percentages were increased after treatment (P < 0.05), while MyD88, TLR4, and NF-κB p65 expressions were decreased (P < 0.05).Conclusions The combination of acupuncture and medicine restored the olfactory function and reduced inflammation in viral- infectious olfactory dysfunction patients, and the curative effect was better than that of the simple drug group. Its mechanism is related to the inhibition of TLR4/MyD88/NF-κB pathway.