Abstract： Objective To investigate the effect of hypoxia on the expression of matrix metalloproteinase(MMP) and tissue inhibitors of matrix metalloproteinase (TIMP) in human periodontal ligament fibroblasts(HPDLF).Methods HPDLF were cultured in α-minima essential medium(α-MEM) and subcultured at confluence. In the hypoxic groups,cells were incubated in a humidified atmosphere of 1％O2,5％CO2,94％ N2 at 37 ℃ for 12,24 and 48 h,respectively.In the normoxic control group,cells were incubated under normoxic conditions of 20％ O2,5％ CO2,75％ N2.The mRNA expression of MMP and TIMP was measured using reverse transcription-polymerase chain reaction (RT-PCR).The data was analyzed by Student's t test,one-way ANOVA and LSD test with SPSS 13.0 software package. Results The expression of MMP-2,TIMP-1 and TIMP-2 mRNA in the hypoxia groups was higher than that in control.The expression of MMP-2 mRNA in hypoxic groups showed a significantly increasing trend.There was significant difference between the hypoxic group and the normoxic control group in the expression of MMP-2 mRNA in HPDLF(P ＜ 0.01 ).The expression of TIMP-1,TIMP-2 mRNA in hypoxic groups of 12 h was momentarily increased. There was significant difference between the hypoxic 12 h group and the normoxic control group in the expression of TIMP-1,TIMP-2 mRNA in HPDLF( P ＜0.05 ).However,with prolonged hypoxia time,the expression of TIMP-1,TIMP-2 mRNA in hypoxic groups showed a significantly declining trend,there were significant differences between the hypoxic 12,24 and 48 h group and the normoxic control group in the expression of TIMP-2 mRNA in HPDLF( P ＜ 0.05 ).The expression of MMP-1 mRNA in hypoxic groups of 12 h was momentarily decreased and then increased after 24 h of hypoxia.There were significant differences between the hypoxic 48 h group and the normoxic control group in the expression of MMP-1 mRNA in HPDLF(P ＜0.05).There were significant differences between the hypoxic 12 h group and the normoxic control group in the ratio of MMP-1/TIMP-1 mRNA ( P ＜ 0.05 ).The ratio of MMP-2/ TIMP-2 mRNA in the hypoxia group significantly increased compared with normoxic group. There were significant differences between the hypoxic group and the normoxic control group in the ratio of MMP-2/TIMP-2 mRNA(P ＜ 0.05).Conclusions Hypoxia could change the expression of MMP and TIMP mRNA and other relevant growth factors and also lead to the imbalance of MMP-2/TIMP-2 mRNA expression.It is suggested that the imbalance of MMP-2/TIMP-2 expression may be closely correlated with the occurrence and development of periodontal disease and play an important role in the process of periodontal tissue destruction in periodontitis.