In summary, our studies demonstrate that the anti-inflammatory effect of rhFGF21 on focal cerebral ischemia occurs through regulation of both central microglia/macrophages and peripheral macrophages via NF-κB and PPAR-γ signaling pathways, indicating that rhFGF21 is a promising candidate for the treatment of ischemic stroke. The gene discussed is PPARG; the disease is Cerebral ischemia.