Abstract： Objective Metabolomics and radioimmunoassay technologies were used to analyze the effects of acceleration exposure on the levels of human serum metabolites , stress-related hormones and such gastrointestinal regulatory factors as resistin and leptin , so as to provide new scientific evidence for the mechanism of gastrointestinal symptoms in motion sickness .Methods Sixty volunteers were recruited and exposed to abnormal acceleration for 15 minutes by using a 6-degree-of-freedom ship motion simulator .The severity of motion sickness was measured by Graybiel Scale; gas chromatography coupled with time-of-flight mass spectrometry ( GC-TOF/MS ) was used to detect serum metabolites in the human subjects; serum glucocorticoid, adrenaline, arginine vasopressin ( AVP ), insulin, resistin and leptin were detected by radioimmunoassay and ELISA .Results ( 1 ) The incidence of motion sickness was 72%.( 2 ) Acceleration exposure could induce significant changes in the levels of serum metabolites in the subjects , of which glucose and N-dodecanoic acid levels were significantly higher than those before exposure , while L-serine and L-threonine levels were significantly decreased after exposure (P<0.05).(3) Acceleration exposure could cause&nbsp;decrease in the level of serum insulin [ (21.03 ±6.78) mIU/L before exposure,(14.97 ±2.94)mIU/L after exposure], and increase in the level of glucagon , glucocorticoid, epinephrine and arginine vasopressin (AVP) [ (18.06 ±5.72)ng/L,(212.88 ±61.37)μg/L,(88.41 ±35.72)ng/L and(10.80 ±7.30)ng/L before exposure;(20.40 ±5.48)ng/L,(293.34 ±50.91)μg/L,(132.83 ±67.25 )ng/L and(51.35 ±8.24)ng/L after exposure] respectively(P<0.05 or P<0.001).(4) Acceleration exposure could also decrease the levels of gastric inhibitory peptide ( GIP), leptin,resistin, but increase the level of ghrelin [ (170.34 ±82.64) nmol/L,(744.03 ±438.46)μg/L,(6687.96 ±3289.18)μg/L and (136.43 ±74.75) ng/L before exposure;(41.05 ±17.91) nmol/L,(409.95 ±347.95)μg/L,(2615.56 ±1345.61)μg/L and (210.85 ±109.01) ng/L after exposure] respectively(P<0.05 or P<0.01).Conclusions Our study indicated that stress could be induced by acceleration exposure , resulting in significant changes in the levels of stress-related hormones and gastrointestinal regulatory factors , as well as serum metabolites .