In conclusion, IL-22 may be a novel pharmacotherapeutic strategy for the treatment of cardiac hypertrophy induced by angiotensin II to limit the progression of heart failure, downregulate the circulatory IL-22 level, prevent the effects of IL-22 and IL-22R on the heart, and reduce the excessive activation of the STAT3 or ERK pathway. Here, STAT3 is linked to cardiac hypertrophy.