Background: hyperlipidemia is a group of heterogeneous disorders characterized by an elevation of lipids in the blood stream. It accounts for the high danger of coronary heart disease and atherosclerosis which is known as a silent killer. Objectives: The aim of work was to evaluate the possible protective effects of Aphanizomenon flos-aquae (AFA) as a natural hypolipidemic product on the cardiac muscle of adult male albino rats, in comparison with Slimquick as a synthetic hypolipidemic drug and their ability to treat hyperlipidemia or to prevent it. Material and methods: fifty six male albino rats (Rattus albinus) were used and categorized into eight groups (7rats/group) .The 1st group (C) rats were used as a control, the 2nd group (H) rats were treated with high fat diet (HFD) (2% cholesterol) to induce hyperlipidemia for 4 weeks only then scarified, the 3rd group (A) rats were orally administrated with AFA only for 4 weeks(94.5 mg/kg body weight /day), the 4th group (H+A1) rats were treated with HFD enriched with 2% cholesterol for 2 weeks to induce hyperlipidemia and the other 2 weeks were fed on the same HFD plus AFA extract administration, the 5th group (H+A2) rats were treated with HFD diet enriched with 2% cholesterol for 4 weeks to induce hyperlipidemia and then they were fed on normal basal diet (BD) plus AFA extract administration for another 2 weeks, the 6th group (S) rats were orally administrated with Slimquick only for 4 weeks (5 mg orlistat/rat/day), the 7th group (H+S1) rats were treated with HFD diet enriched with 2% cholesterol for 2 weeks to induce hyperlipidemia and the other 2 weeks rats were fed on the same HFD plus Slimquick extract administration, the 8 th group (H+S2) rats were treated with HFD diet enriched with 2% cholesterol for 4 weeks to induce hyperlipidemia and then they were fed on normal basal diet (BD) plus Slimquick extract administration for another 2 weeks. Results: the biochemical parameters showed a highly significant increase in the mean value of LDH and CK in the cardiac muscle fibers of the high fat diet group. Many histopathological and histochemical changes were detected in the cardiac muscles of the high fat diet group. Meanwhile, treatment with AFA or Slimquick ameliorated the biochemical parameters, histological and histochemical results; but using AFA extract arrived to decrease the strong changes which were observed in the cardiac muscle fibers of the high fat diet group more than that observed with Slimquick. Conclusion: Aphanizomenon flos-aquae extract as a natural product and Slimquick as a synthetic drug ameliorated the biochemical, histopathological and histochemical changes in the cardiac muscle of the hyperlipidemic rats. Aphanizomenon flos-aquae extract proved to be a better hypolipidemic agent than Slimquick.