This investigation explored how exercise intensity impacts platelet-mediated interactions of nasopharyngeal carcinoma cells (NPCs) and vascular endothelial cells (ECs) under shear flow in 33 males. Our results showed that (a) platelet-NPC aggregates (PNA) were associated with higher shear-induced P-selectin expression and glycoprotein alpha(II)beta(3) activation than platelet-platelet aggregates (PPA); (b) strenuous exercise (SE, up to VO2max), but not moderate exercise (ME, 60% VO2max for 30 min), increased both PPA and PNA in mimicked venous and arterial circuits and enhanced PNA in mimicked flow of stenotic vessels; (c) the percentages of PNA that remained bound to ECs in mimicked flow of post-capillary venules increased, while platelet-induced CD44 cleavage on NPC and trans-endothelial migration of NPC were enhanced following SE, but were unchanged in response to ME. We conclude that SE, but not ME, enhances the capacity of PNA to adhere to ECs, withstand flowing blood, and facilitate the invasion of NPCs toward ECs.