The CD47/SIRPα innate immune checkpoint plays a critical role in regulating tumor immune escape. GW501516, a peroxisome proliferator-activated receptor delta (PPARδ) agonist, is known to promote cancer cell metabolism, proliferation, and inflammation; however, its regulatory mechanism in colon tumor immune escape remains unclear. In this study, qPCR analysis revealed that GW501516 treatment upregulated CD47 gene expression in colon cancer cells. Additionally, GW501516 increased membrane-associated CD47 protein levels in these cells. Mechanistically, luciferase reporter assays demonstrated that GW501516 enhanced CD47 gene transcription activity in colon cancer cells. Co-culture experiments with macrophages further showed that GW501516 treatment suppressed macrophage phagocytic capacity. Crucially, PPARδ knockout abolished GW501516-induced CD47 expression, indicating PPARδ dependency. In vivo implanted tumor models demonstrated that GW501516 facilitated tumor immune escape, whereas PPARδ loss reversed this effect. Collectively, these findings suggest that GW501516 activates PPARδ to promote colon tumor immune escape via CD47 upregulation.