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This study examined the effects of retinoic acid (RA),PD98059,SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrixmetalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in premature rat lung fibroblasts (LFs).LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 (ERK1/2),SP600125 (JNK1/2) and SB203580 (p38) respectively.The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).MMP-2 activity was measured by zymography.The amount of p-ERK1/2,REK1/2,p-JNK1/2,JNK1/2,p-p38 and p38 was determined by West blotting.The results showed that:(1) PD98059,SP600125 and SB203580 significantly inhibited p-ERK1/2,p-JNK1/2 and p-p38 respectively in LFs; (2) The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA,SP600125 and SB203580 respectively (P＜0.01 or 0.05),but did not change after treatment with PD98059 (P＞0.05).Meanwhile,RA,PD98059,SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P＞0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P＞0.05),but decreased remarkably after hyperoxia (P＜0.01 or 0.05).SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P＜0.01).PD98059 exerted no effect on the expression of pro- and active MMP-2 (P＜0.05).It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.