PURPOSE: Major depressive disorder (MDD) is a global health concern. Studies have demonstrated that oleanolic acid (OA) has a regulatory effect on MDD. However, OA is poorly soluble, has low oral bioavailability, and faces challenges in crossing the blood-brain barrier. In this study, building upon a previous formulation of OA cubic liquid crystal nanoparticles (OA-LCNP), we combined nanoparticles with a thermosensitive gel for nasal administration and investigated the pharmacological effects of OA-LCNP thermosensitive gel (OANG) on depression. This study aimed to evaluate the effects of OANG on depression symptoms in rats. METHODS: OANG was prepared using Poloxamer F127 and F68 as the gel matrix, and the ratios of F127 and F68 were investigated. The pharmacokinetics of OANG was studied in rats, and OA content was determined using liquid chromatography-mass spectrometry (LC-MS). The pharmacological effects of OANG on depression were evaluated in chronic unpredictable mild stress (CUMS) model rats. RESULTS: The phase transition temperature of the gel was 34°C, and the release of OA from OANG was slow according to the Higuchi kinetic equation. The AUC CONCLUSION: The OANG nasal drug delivery system has specific brain-targeting properties and exerts anti-depressant effects.