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Control of blood microflow is crucial for the prevention and therapy of blood disorders, such as cardiovascular diseases and their complications. Conventional control strategies generally implant exogenous synthetic materials into blood vessels as labeling markers or actuating sources, which are invasive and incompatible with biological systems. Here, a label‐free, noninvasive, and biocompatible device constructed from natural red blood cells (RBCs) for controlling blood microflow in vivo is reported. The RBCs, optically manipulated, arranged, and rotated using scanning optical tweezers, can function as an optofluidic switch for targeted switching, directional enrichment, dynamic redirecting, and rotary actuation of blood microflow inside zebrafish. The regulation precision of the switch is determined to be at the single‐cell level, and the response time is measured as ≈200 ms using a streamline tracking method. This in vivo optofluidic switch may provide a biofriendly device for exploring blood microenvironments in a noncontact and noninvasive manner. [ABSTRACT FROM AUTHOR]