We found that liver‐specific overexpression of RAGE caused significant macrophage infiltration and expression of pro‐inflammatory cytokines in the liver of middle age mice, while liver‐specific knockdown of RAGE decreased macrophage infiltration and expression of pro‐inflammatory cytokines in the liver of old mice, suggesting that macrophage infiltration and sequential pro‐inflammatory cytokine expression are required for RAGE's effects on old mice hepatic steatosis. The gene discussed is AGER; the disease is fatty liver disease.