This study aimed at evaluating the effects of omega-3-polyunsaturated fatty acids(ω-3-PUFAs) on isoprenaline (ISP) induced rat myocardial fibrosis.Methods: Thirty-two rats were included and divided into 5 groups: Group I(control group) included 8 rats. Group II (omega-3 group): 5rats received oral ω-3-PUFAs at a dose of 40 mg/ kg /day for 8 weeks. Group III (ISP group): 5rats receivedISP at dose of 5 mg/kg /day S.C for 4 consecutive days. Group IV (ISP-recoverygroup): 5rats received ISP at a dose of 5 mg/kg /day S.C for 4 consecutive days thenscarified at the 18th day from ISP injection. Group V (omega-3&ISP group): 5ratsreceived oral ω-3-PUFAs at a dose of 40 mg/kg/day for 8 weeks before subcutaneousISP administration for 4 consecutive days. CPK-MB blood level was measured at theend of the experiment. Myocardial sections were stained with H&E, Masson'strichrome and immunohistochemichal stain for α-SMA. The mean area % of collagenfibers and immunopositive cells were measured.Results: Group II showed non significant difference in the mean CPK-MB bloodlevel compared to the control rats. H&E stained myocardial sections revealed similarhistological architecture of the myocardium as in control group. The statisticaldifference of the mean area % of collagen and α-SMA immunoreactivity was nonsignificant as compared with the control. Group III showed significant increased inthe mean CPK-MB blood level compared to the control group. The H&E stainedmyocardial sections revealed disorganized myocardial tissue and fibrosis withsignificant increase in the mean area % of collagen and α-SMA immunoreactivitycompared to the control. Group VI showed progression of the myocardial injury withsignificant increase in the mean CPK-MB blood level, area % of collagen and α-SMAimmunoreactivity compared to the control. Group V showed significant decrease inthe mean CPK-MB blood level with decrease in the histological alterations caused byISP. There was significant decrease in the mean area % of collagen and α-SMAimmunoreactivity compared to the ISP group.Conclusion: ω-3-PUFAs have cardioprotective effect against ISP inducedmyocardial fibrosis.