Aim To investigate the effect of angiotensin converting enzyme (ACE) antisense cDNA on the synthesis of collagen of the cardiac fibroblasts (Fbs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Methods In vitro, Fbs from SHR and WKY rats was transferred with target ACE antisense cDNA (AS),ACE tuncated cDNA (TS) and empty vector (control) mediated by liposome. Two days after transferation, the target gene expression and the effect on ACE expression was evaluated with reverse transcription polymerase chain reaction, and the target ACE activity of the cells was tested with test reagent. The collagen synthsis of Fbs was tested with 3 H-proline incorporation. Results The expression of ACE antisense cDNA could be detected in Fbs,and the expression peak was in the fourth day after transfection, and it was concomitant with the decrease of ACE expression. This was associated with a significant decrease in ACE activity (14.23±1.62 vs 26.53±2.50 u/10 5 cells,p<0.05) level in target cells and culture medium. However, there was not same effect on Fbs from WKY. AS group had significantly lower 3 H-proline incorporation rate in Fbs from SHR than TS and control group (4 355.7±75.9 vs 6 310.3 ±98.9, 6 529.5±192.5 cpm/10 5 cells, p<0.01). Conclusions ACE antisense cDNA can inhibit the higher basal collagen synthesis in Fbs. Present finding suggests that ACE antisense cDNA will be useful and possible in the gene therapy of higher collagen synthesis related disease and cardiovascular remodeling.