Abstract: Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV₂). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV₂. In situ hexagonal liquid crystals (ISH₂) were prepared based on the composition of ISV₂ with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV₂ and ISH₂ in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV₂ and ISH₂ were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH₂ in adjuvant-induced arthritis rats. The optimal ISV₂ (PT/ET/water, 64:16:20, w/w/w) loaded with 6 mg·g^-1 of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV₂ was able to sustain the drug release for 144 h. The optimal ISH₂ system was prepared by addition of 5% VitEA into PT in the optimal ISV₂ system. This ISH₂ (PT/VitEA/ET/water, 60.8:3.2:16:20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH₂ was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC_0-∞ of ISH₂ group were increased significantly compared with that of SMH solution group and the AUC_0-∞ of ISH₂ group was 6.01 times higher than that of SMH solution group. The developed ISH₂ was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis.