Abstract: OBJECTIVE To prepare risperidone nanosuspension in situ gel and investigate the release behavior of risperidone in vitro. METHODS Risperidone nanosuspension was prepared by anti-solvent precipitation method. Regarding the particle size as index, the formulation and preparation of risperidone nanosuspension was optimized by orthogonal test with the concentration of risperidone(A), the concentration of docosahexaenoic acid (B), the ratio of water phase to oil phase(C) and the roter speed(D) as factors. And the risperidone nanosuspension was characterized. Then risperidone nanosuspension in situ gel was prepared and the release behavior of risperidone was studied. RESULTS The optimized formulation was as follows: A 5 mg·mL^-1, B 10 mg·mL^-1, C 1∶1, D 600 r·min^-1. The mean particle size of risperidone nanosuspension was 176 nm, PI 0.19, Zeta potential -22.4 mV. Under the scanning electron microscope, risperidone was nanocrystal with rod-like morphology. The stability of risperidone nanosuspension was preferable at 4 ℃ after 3 months. In vitro dissolution showed that compared to the rude material, the dissolution rate was improved markedly. In the nanosuspension in situ gel with 20% Poloxamer 407, the release behavior of risperidone conformed to the Higuchi model and the cumulated release was >90% in 30 d. CONCLUSION Risperidone nanosuspension with preferable stability is successfully prepared, and the further prepared nanosuspension in situ gel possesses favorable sustained-release effect.