Short-term efficacy and safety of prednisone in herpes zoster and the effect on IL-6 and IL-10 were investigated. A total of 125 patients (aged 40–70 years) with acute infective herpes zoster who were admitted to Daqing Oilfield General Hospital were selected and divided into 3 groups according to different treatment methods: low-dose (n=44), middle-dose (n=42) and high-dose (n=39) groups. The therapeutic effect, visual analogue scale (VAS) pain score, pain relieving and disappearing time, herpes stopping and disappearing time, incrustation and decrustation time, and incidence of adverse reactions in the three groups were recorded. The changes of IL-6 and IL-10 levels in the peripheral blood of patients before and after treatment were detected by enzyme-linked immunosorbent assay (ELISA) in order to analyze their relationship with pain degree and the time of symptom remission and subsidence. There were no significant differences in cure rate, significant effective rate, effective rate, ineffective rate and total effective rate among the three groups (P>0.05). The pain relieving and disappearing time in the middle-dose group were shorter than those in the low- and high-dose groups (P<0.05). The levels of IL-6 and IL-10 showed no statistical differences in the 3 groups before treatment (P>0.05). Pearson correlation analysis showed that IL-6 was positively correlated with VAS pain score, pain relieving and disappearing time, herpes stopping and disappearing time, incrustation and decrustation time (P<0.05), while IL-10 was negatively correlated with the above indicators (P<0.05). In conclusion, middle-dose prednisone has similar short-term efficacy to high-dose prednisone in the treatment of herpes zoster, but with lower complication and higher safety. IL-6 and IL-10 are closely related to the pain degree and the time of symptom remission and subsidence, which may provide a reference for clinical evaluation of the therapeutic effect of patients with herpes zoster.