AIM To study the molecular mechanisms of retinoic acid (RA) regulating the expression of collagen produced by lung fibroblasts in vivo. METHOD Rats were divided into control, fibrosis and treatment groups and killed at d 28 after bleomycin administration. The lungs were dissected and cultured for lung fibroblasts. The primarily cultured fibroblasts from different groups were used for determination of levels of procollagen α 1(I) mRNA by Northern blot and the content of collagen protein by < 3H> proline incorporation assay. The nuclear protein of fibroblasts was also extracted and used for measurement of AP 1 activity by Gel mobility shift assay. The mRNA levels of retinoic acid receptors were determined by RT PCR. RESULT RA induced the expression of RXRα mRNA and down regulated the AP 1 activity which was enhanced in the fibroblasts from fibrosis groups. RA also greatly reduced both the levels procollagen α 1(I) mRNA and the content of collagen protein which were obviously increased in the fibroblasts from rats of fibrosis group. CONCLUSION The enhanced AP 1 activity may play an important role in mediating the overexpression of collagen protein by fibroblasts from fibrosis group. RA reduces the level of procollagen α 1(I) mRNA of fibroblasts by inducing the expression of RXRα which is known to be able to antagonize AP 1 activity.