Aim: To develop a novel, in situ gel system for nasal delivery of scopolamine hydrohromide (SCOP) and study its efficacy on motion sickness. Methods: SCOP in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared,respectively, and characterized in terms of viscosity, in vitro release, and nasal ciliotoxicity. Single photon emission computing tomography technique was used to evaluate the nasal residence time of gel containing 99mTc tracer. The antimotion sickness efficacy produced by the in situ gel formulation was investigated in rats and compared with those achieved after subcutaneous and oral administration.Results: The viscosity of the gellan gum formulations either in solution or in gel increased with increasing concentrations of gellan gum. Its release in vitro was moderate in artificial nasal fluid. The micrographic results showed that in situ gels were safe, without nasal ciliotoxicity. In comparison with phosphate buffer saline,a prolonged radioactivity of 99mTc in the rabbit nasal cavity was observed after administration of the gellan gum formulation. Intranasal SCOP in situ gel at a dose of 100 μg/kg decreased symptoms of motion sickness significantly in comparison with subcutaneous and oral administration (P＜0.01). Conclusion: SCOP nasal in situ gel is a safe and promising therapeutic alteative to existing medications for motion sickness.