Background Aqueous two-phase extraction has advantages of green extraction, high yield, good product purity and low cost. However, conventional aqueous two-phase systems (ATPSs) are limited in extraction/separation due to high polarity. Some researchers tuned the hydrophobicity of ATPSs by addition of hydrophobic ionic liquids or polymers. We aimed to tailor the hydrophobicity of a solvent-salt-water ATPS using cosolvent for extraction of paeonol from cortex moutan. Results Tie-line length and compositions in the ATPS were employed for qualitative evaluation of polarity and polarity difference between the two phases. Conditions such as pH, salt type and concentration, total solvent volume fraction and cosolvent fraction were optimized. Ethyl acetate (EA) as cosolvent in ethanol-NaH2PO4-H2O (EtPO) system did not alter the first-order kinetic extraction model, but it improved the kinetic constant and boosted the partition coefficient from 36.7 to 58.8. For both EtPO and EtPO-EA systems, both the extraction yields and partition coefficients increased when temperature increased from 11 to 37 degrees C. The optimized EtPO-EA system demonstrated higher extraction yield than EtPO and 70% (v/v) ethanol systems by 25.4 and 19.5%, respectively. Conclusions The hydrophobicity of an ATPS was successfully tuned with cosolvent for paeonol extraction. The cosolvent-salt-water two-phase systems are promising in extraction of weakly polar components from herbs. (c) 2019 Society of Chemical Industry