The present work was conducted to optimize and evaluate poloxamer (P407 and P188)-based Angelicae Dahuricae Radix and Chuanxiong Rhizoma intranasal in situ gels (ZXS gel).The ZXS volatile oil was obtained by steam distillation and the extract was collected by 95% ethanol and purified by macroporous resin HPD 100.In situ gels were prepared by freezing dissolve method and a two-factor central composite design was employed to optimize the matrix formulations.The optimized formulations were selected and investigated the in vitro release properties, nasal mucosal permeability, effects on migraine rats and ciliotoxicity.In this study, a matrix formulation consists of 20% P407 and 6.5% P188 was obtained with a gelation temperature of 30.4 ± 0.6℃ (after drug-loaded) and enhancement of nasal mucosal permeability.Via intranasal administration the ZXS gel was able to alleviate migraine symptoms effectively and quickly, and maintain brain 5-HT content at a normal level (Fig.1).Following the exposure of ZXS in situ gel to toad upper palate mucosa for 30min, the ciliary morphology and movement were hardly affected.Thus, the ZXS intranasal in situ gel is potentially in clinical use for the treatment of migraine.