The role of membrane aquaporin-1 (APQ-1) in the photobiomodulation (PBM) on erythrocyte deformability will be studied in this paper with human dehydrated erythrocytes as echinocytic shape alterations lead to decreased cellular deformability. Human dehydrated erythrocytes were irradiated with low intensity He-Ne laser irradiation (LHNL) at 0.9, 1.8, 2.7, and 4.4 mW/cm2 for 5, 15, and 30 min, respectively, and APQ-1 inhibitor, 0.2 μmol/L HgCl2, was used to study the role of APQ-1 in mediating PBM with LHNL at 4.4 mW/cm2 for 5 min. Comprehensive morphological parameters of an intact cell such as contact area, perimeter, roundness and erythrocyte elongation index (EEI) were measured to characterize erythrocyte deformability with fast micro multi-channel spectrophotometer. It was observed that the dosage of LHNL improvement of the morphological parameters of dehydrated erythrocytes was morphological-parameter-dependent, but the Bunsen-Roscoe rule did not hold for roundness. The LHNL at 4.4 mW/cm2 for 5 min significantly improved the contact area (P<0.05) and EEI (P<0.05) of the dehydrated erythrocytes, but the improvement was significantly inhibited by 0.2 μmol/L HgCl2 (P<0.05). It was concluded that AQP-1 might mediate the effects of LHNL on erythrocyte deformability, which supports the membranotropic mechanism of PBM.