The present work was designed to establish a novel animal model for motion sickness (MS) in rodents and to evaluate the effects of a combination of scopolamine and modafinil on MS with this novel method. It was found that the rats and mice presented several symptoms induced by rotation such as, piloerection, tremble, urinal and fecal incontinence. As the rats and mice are lack of emesis response to rotation, we used a score based on abovementioned symptoms as an index for the severity of MS in rodents. MS index was determined in 260 mice with this novel method. It was found that the distribution of MS index was normal (W=0.99; P=0.23. P>0.05 considered values' normal distribution). The effects of scopolamine on MS were studied in mice and rats. It was found that scopolamine significantly decreased MS index at the dose of 0.3 mg/kg in mice and 1.0 mg/kg in rats. Finally, the effects of a combination of scopolamine and modafinil were observed with this novel method in rats. It was found that the efficacy of the combination (5.0+5.0 mg/kg) was greater than the single drugs (10 mg/kg). Even the smallest dose of the combination (0.5+0.5 mg/kg) had a similar effect to large dose of scopolamine or modafinile when they were used alone. In conclusion, this animal model is suitable for MS study in rats and mice and the combination of scopolamine and modafinil might be a new method to treat or prevent MS.