Abstract: To provide basic research data for understanding the changes of metabolic enzymes under weightlessness, the effect of simulated microgravity on hepatic CYP1A2 in rats was investigated. After the rats are tail suspended for 3, 7, 14 and 21 days, the protein expression, mRNA expression and the CYP1A2 activity were detected by western-blot, Q-PCR and HPLC-UV methods. Compared with the control group, the expression of CYP1A2 protein decreases significantly (p<0.05) in the 3 d tail suspended (TS) rats, but increases significantly (p<0.05) in the 7 and 14 d TS rats. The expression of protein decreases slightly (p> 0.05) in the 21 d TS rats. The mRNA expression and activity of CYP1A2 increase significantly (p<0.05) in 3, 7 and 14 d TS rats and increase slightly (p> 0.05) in 21 d TS rats compared with the control group. The 14 d simulated group has the most significant effect on the expression and the activity of hepatic CYP1A2 in rats. All the indices in 21 d TS rats show the tendency to the control group level. This study provides basic research data for understanding changes of metabolic enzymes and drug safety of astronauts under the microgravity condition.