The precise mechanism which leads to fibroproliferative changes in bronchopulmonary dysplasia (BPD) is poorly understood. C-myc proto-oncogene has been associated with proliferation of fibroblasts in scleroderma. Objective: This study is to determine whether the antisense ON of c-myc proto-oncogene inhibits the proliferation of human neonatal lung fibroblasts. Method: Antiproliferative effect of an unmodified 15-mer c-myc antisense ON on the cultured lung fibroblast (CCD-32 Lu) was investigated utilizing a nonviral cationic lipid gene delivery system, LipofectinR, which consists of DOTMA:DPE 1:1. In vitro proliferation of lung fibroblasts with c-myc antisense ON delivered by Lipofectin was compared to the two control groups, with c-myc antisense ON alone and without c-myc antisense ON, by MTT cell proliferation assay. Result: Two control groups did not differ in the magnitude of fibroblast proliferation(p>0.05). Compared to the controls, the group with c-myc antisense ON delivered by Lipofectin showed a reduction of 42.5% (SD, 2.4) in cell proliferation (p<0.05). Conclusion: Our study suggests that the c-myc antisense ON delivered into the fibroblast suppresses its proliferation by the sequence specific inhibition of the mRNA of c-myc proto-oncogene. Speculation: This antisense strategy with an efficient gene delivery system, may potentially lead to a new therapeutic approach for the inhibition of pulmonary interstitial fibrosis associated with BPD.