There was a significant positive correlation between IL-21 and STAT3 and p-STAT3 expression in cholesteatoma and granuloma tissues, suggesting that IL-21 may be acting on cholesteatoma and granuloma through STAT3 signaling pathway, but there was no significant difference in the positive expression rate of IL-21 in cholesteatoma and normal external ear canal skin tissue; therefore, it is not considered to have a significant effect on the proliferation of cholesteatoma keratinocytes, so IL-21 may play an important role in the chronic inflammation of the middle ear. This evidence concerns the gene STAT3 and Granuloma.