The studying of water transport across the red blood cell (RBC) membrane holds great significance in understanding cellular physiology and pathophysiology, developing therapeutic strategies, and designing drug delivery systems. Important advancements have been achieved in the investigation of experimental methodologies, regulatory factors, and comparative analyses of RBC from different species; nevertheless, there is still room for improvement. Aquaporins (AQPs) are a family of integral membrane proteins that mediate water transport and play a prominent role in regulating water movement in the body. Among them, aquaporin-1 (AQP1) is the major type located on the RBC membrane. Due to its unique structure, especially the water pore, AQP1 exhibits high selectivity for water permeability, which is essential for the physiological functions of RBC. There are different opinions on whether AQP1 mediates the transport of carbon dioxide (CO2) and hydrogen peroxide (H2O2), with experimental results supporting each aspect. Abnormalities in RBC AQP1 have been closely associated with the occurrence and development of various clinical diseases. Therefore, studying the physiological functions of AQP1 in RBC serves as a foundational basis for unraveling the pathological mechanisms underlying these diseases and provides potential novel drug targets. This chapter reviews recent research progress on water transport across the RBC membrane from multiple dimensions, aiming to provide ideas and references for basic research and the prevention and treatment of diseases. By in-depth exploring the research pertaining to water permeability in RBC, our comprehension and utilization of their functional attributes can be significantly augmented.