The expression of the "pro-inflammatory" cytokines interleukin (IL) -1 and -6 is induced after myocardial ischemia, but the pathophysiological role of these cytokines is largely unknown. In this study the effect of IL-1 receptor antagonist was analyzed after ischemia/reperfusion (IR) in rats. Methods: Myocardial ischemia was induced in 12 weeks old female Sprague-Dawley rats by ligation of the left coronary artery. After 60 min reperfusion was established and treatment with IL-1 receptor antagonist (rhIL-1ra, Kineret®, 3 x 33 mg s.c., IR-K)) or NaCl (IR) started. Heart function was measured with Millar-tip catheters after 5, 10, 24 and 72 h of reperfusion (n=5–8 in each group). Thereafter, the hearts were analyzed for mRNA expression (RPA), MMP activity (zymography) and protein expression/-phosphorylation (Western). Results: Myocardial function after IR improved by IL-1ra treatment (after 72 h: LVEDP 13±1 vs. 9±1 mmHg, LVdP/dtmax 7658±360 vs. 9138±599 mmHg/s, LVtau 13.8±0.5 vs. 11.7±0.3 ms, HMV 72±6 vs. 92±9 ml/min in IR vs. IR-K, respectively, for all p<0.05). This was associated with reduced MI size (TTC/Evans Blue staining after 24 h: 64±7 vs. 37±5 % MI/AAR in IR vs. IR+K, each n=3, p<0.05). Furthermore, there was increased Akt phosphorylation but reduced mRNA expression of FAS Ag, bax and Caspase 3 as well as of bcl-x and IL-6. In contrast, MMP-8/-9 expression as well as MMP-9 activity was unchanged indicating comparable cell infiltration.