A phenol-4, 4′-diaminodiphenyl methane-based benzoxazine (P-ddm)/N,N′-(1,1,2-trimethylhexane-1,6-diyl) bis (maleimide) (TBMI)/imidazole blend with bi-continuous phase structure was prepared. The phase structures, reaction mechanism and kinetic parameter of P-ddm/TBMI/imidazole were researched, and the influence of chemical structural differences on phase structure was discussed based on the calculated Flory-Huggins parameters. P-ddm/TBMI/imidazole had a bi-continuous phase structure while bisphenol A-aniline-based benzoxazine (BA-a)/TBMI/imidazole had a homogeneous one. The Flory-Huggins parameter of P-ddm/TBMI/imidazole was 0.048, which was lower than that of BA-a/TBMI/imidazole. However, since the amount of reacted P-ddm was higher than that of BA-a at lower temperature (120 °C), the critical Flory-Huggins parameter of P-ddm/TBMI/imidazole decreased faster than that of BA-a/TBMI/imidazole did. Therefore, P-ddm/TBMI/imidazole was unstable from the thermodynamic point and more prone to phase separation than BA-a/TBMI/imidazole. Fitting of viscosity curves at different temperatures showed that P-ddm/TBMI/imidazole had excellent mobility which benefited the formation of bi-continuous structure. The better mobility of P-ddm/TBMI/imidazole may be caused by methylene in P-ddm. Compared with isopropylidene in BA-a, this structure had less hindrance effects on molecular flow, which may be the key point in phase separation.