A detailed phase transition process of poly(2-isopropyl-2-oxazoline) (PIPOZ) in aqueous solution was investigated by means of DSC, temperature-variable H-1 NMR, Raman, optical micrographs, and FT-IR spectroscopy measurements. Gradual phase separation accompanied by large dehydration degree and big conformational changes above the lower critical solution temperature (LCST) and facile reversibility were identified. Based on the two-dimensional correlation (2Dcos) and perturbation correlation moving window (PCMW) analyses, the sequence order of chemical group motions in phase transition process was elucidated. Additionally, a newly assigned CH3 center dot center dot center dot O=C intermolecular hydrogen bond at 3008 cm(-1) in the PIPOZ system provides extra information on the interactions between C-H and C=O groups. The formation of cross-linking "bridging" hydrogen bonds C=O center dot center dot center dot D-O-D center dot center dot center dot O=C (1631 cm(-1)) is proposed as the key process to induce the liquid-liquid phase separation and polymer-rich phase formation of PIPOZ solution. With slow heating, more and more "bridging" hydrogen bonds were formed and D2O were expelled with an ordered and mostly all-trans conformation adopted in the PIPOZ chains. On the basis of these observations, a physical picture on the molecular evolution of PIPOZ solution during the phase transition process has been derived.