Background: Nigella sativa (NS) has anti-inflammatory and antioxidant activity; it exhibits a role in tissue fibrosis and wound healing. Angiotensin-converting enzyme (ACE) inhibitors improve the cardiac fibrosis. This study aimed to evaluate the effect of Nigella Sativa and ACE inhibitors and combination of both on myocardial fibrosis induced by lipopolysaccharide. Material and methods: Thirty-five male albino rats were divided into five groups. 1. Control group 2. LPS group in which rats were injected intraperitoneally (IP) with lipopolysaccharide (LPS) at a dose of (1 mg/kg/day) daily for three weeks. 3. NS treated group in which rats were IP injected with LPS then given NS oil orally at a dose of (1ml/ day) daily for three weeks 4. Captopril (CAP) treated group in which rats were IP injected with LPS then given CAP orally at a dose of (100 mg/kg/ day) daily for three weeks. 5. NS&CAP treated group in which rats were IP injected with LPS then given NS and CAP. Then the left ventricular tissues were examined for histopathological and immunohistochemical changes. Results: LPS induced loss of architecture of the cardiomyocytes with marked fibrosis indicated by significant increase in area % of collagen fibrosis and α-SMA immunostaining expression. NS and CAP improved these changes but the combination of both revealed marked improvement of the histopathological changes with significant decreasing in area % of collagen fibrosis and α-SMA immunostaining expression. Conclusion: we concluded that the combination of Nigella sativa and Angiotensin-converting enzyme inhibitor markedly improved the myocardial fibrosis induced by lipopolysaccharide